The pituitary gland in horses is a small, yet significant endocrine organ located at the base of the brain. It is responsible for producing and releasing hormones that regulate various physiological processes, including growth, metabolism, and reproduction. The gland is divided into two main parts: the anterior pituitary, which secretes hormones such as adrenocorticotropic hormone (ACTH) and growth hormone (GH), and the posterior pituitary, which releases hormones like vasopressin and oxytocin. Changes or dysfunctions in pituitary function can lead to conditions such as pituitary pars intermedia dysfunction (PPID), commonly known as equine Cushing's disease, which affects older horses. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and clinical implications of the pituitary gland in equine health.
Bousfield GR, Butnev VY, Gotschall RR, Baker VL, Moore WT.There are two species for which both pituitary and placental gonadotropins are readily available, humans and horses. The human gonadotropins are better characterized than equine gonadotropins. Nevertheless, the latter are very interesting because they provide exceptions to some of the general structure-function principles derived from studies on human and other mammalian gonadotropins. For example, separate genes encode the hLH beta and hCG beta subunits while a single gene encodes eLH beta and eCG beta. Thus, eCG and eLH differ only in their oligosaccharide moieties and eLH is the only LH tha...
Bettschart-Wolfensberger R, Taylor PM, Sear JW, Bloomfield MR, Rentsch K, Dawling S.To examine the physiologic and pharmacokinetic effects of a technique of total intravenous anesthesia in ponies. Methods: 6 healthy ponies. Methods: Ponies were premedicated with acepromazine (0.03 mg/kg of body weight, IV) and xylazine (1.0 mg/kg, IV). Two minutes later, anesthesia was induced with ketamine (2.0 mg/kg, IV) followed by climazolam (0.2 mg/kg, IV). Anesthesia was maintained for 120 minutes by an infusion of climazolam (0.4 mg/kg/h) and ketamine (6.0 mg/kg/h). Oxygen (5 L/min) was supplemented. 20 minutes after the infusion was stopped sarmazenil (0.04 mg/kg, IV) was administered...
Muñoz MC, Doreste F, Ferrer O, González J, Montoya JA.A 16-year-old, male, Hanoverian horse had a three-month history of weight loss, hirsutism and polyuria/polydypsia. Examinations revealed neutrophilia, lymphopenia, hyper glycaemia and abnormalities in hepatic function. A tentative diagnosis of hyperadrenocorticism was made. The results of thyroid-releasing hormone and combined dexamethasone suppression and ACTH stimulation tests suggested the presence of a pituitary adenoma. The horse was treated with pergolide and beneficial clinical and biochemical responses were observed within one to six months.
Butnev VY, Gotschall RR, Baker VL, Moore WT, Gout PW, Bousfield GR.Glycosylated equine prolactin (G-ePRL) and nonglycosylated ePRL were purified to homogeneity from side fractions obtained during isolation of LH/FSH from horse pituitaries. Both PRL forms were isolated together in high yield by the isolation procedure used for glycosylated porcine PRL/(G-pPRL) and pPRL, involving acetone extraction/precipitation, NaCl and isoelectric precipitation, and gel filtration. Purification of G-ePRL required additional Con A chromatography. The N-terminal amino acid sequencing for 32 cycles of G-ePRL and ePRL resulted in sequences identical to the known primary structu...
Brinsko SP.Poor fertility has been associated with hormonal imbalances in the stallion. The primary cause of this imbalance is unknown, but it may be related to abnormal gonadotropin secretion. Secretion of GnRH from the hypothalamus causes the release of LH and FSH from the anterior pituitary and these gonadotropins help maintain adequate steroid levels so that normal spermatogenesis can occur. Hypogonadotropic hypogonadism has not been documented in the stallion; however, GnRH therapy has improved the fertility of a limited number of horses. Downregulation of the HPT axis readily occurs in most other s...
Evans MJ, Mulligan RS, Livesey JH, Donald RA.Perifused equine anterior pituitary cells were used to investigate the relationships between the secretion of ACTH and substances known to either stimulate (corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP)) or inhibit (cortisol) ACTH secretion. The experiments were designed to mimic the hormone milieu present in vivo in the horse, with cortisol (0 or 100 nmol/l) and CRH (0 or 0.02 nmol/l) perifused continuously, and pulses of AVP (10 nmol/l) applied for 5 min at 30-min intervals. In columns perifused with 0.02 nmol CRH/l there was no significant overall effect of 100 nmol...
Chopineau M, Stewart F.Reverse transcription-PCR was used to clone the coding region of the donkey (Equus asinus) glycoprotein hormone alpha-subunit transcript from pituitary gland RNA. The donkey alpha-subunit sequence demonstrated considerable identity with the horse (97% at the nucleotide level), confirming the very close evolutionary linkage between these two species. The predicted amino acid sequence revealed that the donkey alpha-subunit has the same unusual C-terminus as the horse alpha-subunit, when compared with all other mammalian alpha-subunits, including a Tyr-His transposition between positions 87 and 9...
Alexander SL, Irvine CH, Donald RA.Since 1985, we have applied our nonsurgical technique for collecting pituitary venous (PitVen) blood from ambulatory horses to investigate the regulation of adrenocorticotropic hormone (ACTH) secretion. This method offers particular advantages for studying the hypothalamo-pituitary-adrenal axis since its benign nature enables hypothalamic and pituitary interactions to be monitored without disturbing the animal, and the horse's large blood volume allows 3- to 4-ml samples to be collected as frequently as every 20s for prolonged periods so that the secretion patterns of ACTH and its secretagogue...
Alexander SL, Irvine CH.We used our nonsurgical method for collecting equine pituitary venous blood to study the role of endogenous opioids in the basal regulation of the hypothalamo-pituitary-adrenal axis. We gave mares the opioid antagonist, naloxone (NAL), at either a high (0.5 mg/kg i.v. bolus, followed by infusion of 0.25 mg/kg.h; n = 4) or low (0.2 mg/kg i.v. bolus; n = 6) dose rate. Pituitary venous blood was collected continuously, divided into 0.5- or 1-min segments for 15-30 min before and 1 h after the NAL bolus, and assayed for CRH, arginine vasopressin (AVP), and ACTH. The mares tolerated NAL administrat...
Silvia PJ, Meyer SL, Fitzgerald BP.Twelve horse mares were used in a repeated-measures design consisting of 3 replicates of 4 mares each. On Day 6 following ovulation, luteolysis was initiated with an i.m. injection of prostaglandin F2 alpha (PGF2 alpha; Lutalyse, 10 mg). Either 12 (-12) or 36 (-36) h before PGF2 alpha (PRE), blood samples were collected simultaneously from the intercavernous sinus (ICS) and jugular (JUG) vein at 10-min intervals for an 8-h period. Pituitary capacity to exogenous GnRH (2 micrograms/kg BW, i.v.) was evaluated at the alternate time point within this period. Frequent sampling and GnRH challenge we...
Chopineau M, Stewart F, Allen WR.The coding regions of the horse (Equus caballus) and donkey (E. asinus) luteinizing hormone (LH) beta-subunit transcripts were cloned from pituitary gland RNA, in order to investigate their relationships to the corresponding equine chorionic gonadotropin (CG) beta-subunits and to further understand the unusual receptor-binding properties of equine LH and CG. The horse and donkey LH beta-subunit sequences were very similar (97% identity at the nucleotide (nt) level; 93% at the amino acid (aa) level), confirming their very close evolutionary linkage and also indicating that the C-terminal extens...
Thompson JC, Ellison R, Gillett R, Badcoe L.Thyrotropin releasing hormone (TRH) stimulation tests were carried out on a number of horses, including one clinically affected horse whose age and clinical signs suggested that a pituitary adenoma was most unlikely. The results of these tests indicated that, according to criteria published overseas, the majority of these horses had pituitary adenomas. The fact that clinically normal or affected horses may have marked increases in cortisol concentrations indicates that the TRH stimulation test is not suitable for the diagnosis of pituitary adenoma. Other tests, including alterations in glucose...
van der Kolk JH, Wensing T, Kalsbeek HC, Breukink HJ.The objective of the study was to determine the sensitivity with which an adenoma of the pars intermedia of the pituitary gland can be predicted in horses by measuring the basal concentrations of glucose, cortisol, adrenocorticotropin (ACTH), and insulin, the urinary concentration of corticoids, the urinary corticoid:creatinine ratio, and the plasma cortisol concentration after the administration of 25 IU of ACTH intravenously. The records of 24 cases of histologically confirmed equine pituitary pars intermedia adenomas were used. An adenoma of the pars intermedia of the pituitary gland in hor...
Luna SP, Taylor PM.The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 1.2 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 1.2 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1.2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration i...
Ellis MJ, Livesey JH, Donald RA.Immunoreactive corticotrophin-releasing hormone (irCRH) was present in methanolic extracts of equine peripheral blood and showed no elevation in maternal peripheral serum in late gestation (0.54 +/- 0.25 pmol/l; mean +/- S.D.) compared with control horses (0.41 +/- 0.15 pmol/l). The irCRH of methanolic extracts of pituitary venous plasma had a similar elution position following reverse-phase HPLC to synthetic human CRH(1-41) and to irCRH released from horse stalk-median eminence tissue incubated in vitro. Gel chromatographic studies showed no evidence for a plasma CRH-binding protein (CRHBP) a...
Müller W, Firsching R.The Magneson and Titan yellow tests were used to detect Mg in amyloid deposits in primary and secondary amyloidosis, in a pituitary tumour and in a case of equine cutaneous amyloidosis. Especially vascular amyloid deposits turned out to contain high levels of Mg. The significance of these findings remains unclear at present. Competition between Mg and Ca, the relationship between Mg in elastic fibres and amyloid P-component, and the high water content of amyloid along with the interaction of Mg with water are discussed.
Ellis MJ, Mulligan RS, Evans MJ, Donald RA.Antagonists are useful for probing hormone action and receptor characteristics. In this study we have investigated the inhibitory effects of analogues of arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) on stimulated release of immunoreactive ACTH from perifused equine anterior pituitary cells in vitro. Our aims were to gain some insight into the characteristics of the CRH and AVP receptors of the horse pituitary and to establish whether the response induced by AVP and CRH together could be blocked by combining antagonists. Experimental design included 5-min pulses of AVP ...
Reilly L, Habecker P, Beech J, Johnston J, Sweeney C, Hamir A.Abscess of the pituitary gland is a rare condition which has been
described in man (Domingue and Wilson 1977; Ahmed et al. 1989),
ruminants (Taylor and Meads 1963; Moriwaki er al. 1973; Lomas and
Hazell 1983; Perdrizet and Dinsmore 1986) and one horse
(Rumbaugh 1977). The some of infection may be either direct
extension from an adjacent focus or haematogenous spread from a site
elsewhere in the body. In man, pituitary abscess may result from
meningitis, sphenoid sinusitis (Selose et al. 1980), and osteomyelitis
(Rongetti and Daniels 1950). A review of 20 cases of pituitary abscess
in ...
Moore BR, Abood SK, Hinchcliff KW.The medical records from 9 consecutive miniature horses (n = 5) and miniature donkeys (n = 4) with hyperlipemia (serum triglyceride concentration > 500 mg/dL) were reviewed. In all cases, hyperlipemia was a secondary complication of a primary systemic disease including septicemia, colitis, parasitism, esophageal obstruction, gastric impaction and rupture, fecalith, and pituitary adenoma. Therapy consisted of specific treatment for the primary disease, supportive care, and nutritional support. The mean time for resolution of hyperlipemia in cases requiring nutritional support (n = 6) was 7 days...
Alexander SL, Irvine CH, Donald RA.To characterize the short-term ACTH secretion pattern and to investigate factors regulating it, pituitary venous (PV) blood was collected using our nonsurgical method from 8 unperturbed horses every 20 or 30 s for approximately 1 h. In all but 1 horse, sampling occurred during the broad circadian maximum in plasma cortisol concentrations. Concentrations of corticotropin-releasing hormone (CRH; n = 7 horses), arginine vasopressin (AVP), ACTH and cortisol were measured by radioimmunoassay. In all horses, CRH, AVP and ACTH secretion patterns appeared irregular in time and amplitude. The mean (+/-...
Aurich C, Schlote S, Hoppen HO, Klug E, Hoppe H, Aurich JE.To investigate an involvement of endogenous opioids in the regulation of circannual changes in reproductive activity, effects of the opioid antagonist naloxone on the concentration of immunoreactive and bioactive luteinizing hormone (LH) in plasma were measured in mares during the anovulatory season. Naloxone (0.5 mg/kg i.v.) caused a significant increase (P < 0.05) in immunoreactive as well as bioactive LH concentration in plasma. The amplitude of the increase in LH concentrations measured with an in vitro bioassay was more pronounced than the amplitude of the increase in LH secretion dete...
Irvine CH, Alexander SL.Conflicting views exist on the mode of gonadotrophin-releasing hormone (GnRH) secretion during the ovulatory LH surge and the relative importance of changes in pituitary responsiveness to GnRH in generating the LH surge. This disagreement may stem from species differences and/or methodological problems. To provide data on the exact relationship between GnRH and gonadotrophin secretion during the spontaneous LH surge, we collected pituitary venous (PV) blood every 30 s for 3-4 h from eight mares and then assayed GnRH (in six of the mares), FSH and LH. Jugular blood was also collected from twelv...
Kemppainen RJ, E Peterson M.Cushing's disease, defined as hyperadrenocorticism resulting from excessive secretion of pituitary ACTH, occurs spontaneously and quite commonly in dogs and horses. In dogs, as in humans, the disease is usually associated with a small tumor of the pituitary pars distalis. However, the disease may arise occasionally (dogs) or exclusively (horses) from tumors or hyperplasia of the pituitary pars intermedia. In dogs, pars intermedia tumors may arise from one of two proopiomelanocortin-containing cell types that are present in normal tissue.
Mumford EL, Squires EL, Jasko DJ, Nett TM.A lack of pituitary LH stores has been implicated as the cause of seasonal anestrus and failure to ovulate during the spring transition period in mares. In this experiment, 40 mares were used to study the effects of GnRH, estrogen, and an estrogen-GnRH combination on increasing releasable pituitary LH. Mares were stratified based on their ability to secrete LH in response to a 950-micrograms challenge of GnRH (n = 10 per group) and then assigned to one of four treatment groups: 1) controls, given no treatment; 2) 1 mg of estradiol-17 beta in oil i.m. daily for 8 d; 3) 200 micrograms of GnRH an...
Cahill CM, Van der Kolk H, Goode JA, Hayden TJ.Highly purified and well-characterised preparations of equine prolactin and growth hormone from equine pituitary glands were employed to set up highly sensitive and specific homologous radioimmunoassays (RIA) for the measurement of hormone in horse plasma. The limit of sensitivity of the GH RIA was 1.2 ng/ml with mean intra- and inter-assay coefficients of variation (CV) of 6.6 and 10%, respectively. The sensitivity of the equine prolactin (ePRL) RIA was 0.5 ng/ml with mean intra and inter-assay CV of 9.1 and 15.6%, respectively. Dose-response curves of a crude pituitary gland extract and plas...
van der Kolk JH, Kalsbeek HC, van Garderen E, Wensing T, Breukink HJ.The records of 21 horses with an adenoma of the pars intermedia of the pituitary gland were reviewed. The animals comprised nine Dutch warmblood horses and 12 ponies. They ranged in age from 12 to 30 years (mean +/- sem 21 +/- 1.3 years) for 20 of the horses, and comprised 13 geldings and eight mares. All the animals showed hirsutism. In 1991, nine horses were diagnosed as having the adenoma, equivalent to 0.5 per cent of the horses examined in 1991. The mean +/- sem survival time of four of the horses (from discharge to the development of complications which required euthanasia) was 192 +/- 5...
Harkins JD, Carney JM, Tobin T.Corticosteroids possess potent anti-inflammatory activity and are commonly injected intra-articularly for local relief of inflammatory lesions in performance horses. However, the suppression of anabolic activity in the joint may lead to an increased rate of joint breakdown. Complications associated with intra-articular corticosteroid therapy include septic arthritis, which is usually due to inadvertent joint contamination at the time of corticosteroid injection, and steroid arthropathy, which is characterized by an accelerated rate of joint destruction and radiographic evidence of severe degen...
Dowling PM, Williams MA, Clark TP.Adrenal insufficiency was diagnosed in a 9-year-old American Quarter Horse gelding that had received monthly injections of stanozolol for 8 years. After the injections were abruptly discontinued, the horse developed anorexia, lethargy, weight loss, and bilateral forelimb lameness. Secondary hypoadrenocorticism was diagnosed on the basis of clinical signs, lack of high endogenous plasma ACTH concentration, and lack of cortisol response to administration of ACTH. Because the medical history did not include glucocorticoid administration, the cause was determined to be excessive administration of ...
Muyan M, Roser JF, Dybdal N, Baldwin DM.The objective of the present study was to determine whether the testicular steroids, i.e., testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and estrone sulfate (E1SO4), play a physiological role in regulating LH release in the male horse by direct actions at the anterior pituitary gland. Enzymatically dispersed anterior pituitary cells from stallions (n = 4) or geldings (n = 3) were cultured for 48 h in alpha-modified Eagle's medium containing 10% steroid-free horse medium. To determine the effects of the steroids on the LH response to GnRH, the cells were incubated f...
Boujon CE, Bestetti GE, Meier HP, Straub R, Junker U, Rossi GL.Clinico-pathological correlations in horses with pituitary adenomas are poorly understood. This paper describes the functional and morphological features of five cases of equine pituitary adenoma and of a case of multinodular pituitary hyperplasia. New findings reported include immunoreactivity for beta-lipotropin (beta-LPH), beta-melanocyte-stimulating hormone (beta-MSH), gamma 3-MSH, prolactin (PRL), and follicle-stimulating hormone (FSH) in neoplastic cells of the pituitary adenoma; and, in the multinodular hyperplasia, beta-LPH, beta-endorphin (beta-END), alpha-MSH, beta-MSH, gamma 3-MSH a...
Evans MJ, Kitson NE, Livesey JH, Donald RA.Perifused equine anterior pituitary cells were used to investigate the effect of cortisol on the ACTH response to pulses of corticotrophin-releasing hormone (CRH; 0.01 nmol/l) and arginine vasopressin (AVP; 100 nmol/l), given for 5 min every 30 min for 690 min and ACTH measured in 5-min fractions. At the fourth pulse of secretagogue (0 min), a constant perifusion with cortisol began (0 nmol/l (control), 100, 200, 500, 5000 and 50,000 nmol/l) and continued until the ninth pulse (150 min). For each pulse of secretagogue, the amount of ACTH (pmol) secreted in response to each pulse (ACTH response...
Thorson JF, Allen CC, Amstalden M, Williams GL.The continuous, subcutaneous infusion of native GnRH into seasonally anovulatory mares stimulates the synthesis and secretion of LH without pituitary refractoriness, offering opportunities to markedly accelerate the timing of ovulation within the operational breeding season. Herein, we tested the hypothesis that ovarian cycles induced in winter anovulatory mares using continuous administration of native GnRH for 28 days, beginning in either early February or early March (North America) would not revert to an anovulatory state after treatment withdrawal. Anovulatory mares received sham pumps (c...
Clay CM, Squires EL, Amann RP, Nett TM.Effects of season and photoperiod on the anterior pituitary gland and testes were studied by responses to exogenous GnRH. Stallions were assigned to one of three treatments: 1) control, exposed to natural day length; 2) S-L, 8 h of light and 16 h dark (8:16) for 20 wk beginning July 16, 1982 then 16:8 from December 2, 1982 until March 5, 1984; or 3) S-S, 8:16 from July 16, 1982 until March 5, 1984. Approximately every 8 wk, stallions were administered GnRH (2 micrograms/kg BW) and blood was sampled at 20-min intervals for 2 h before and 8 h after GnRH administration. Concentrations of LH, FSH ...
Costello J, Firshman AM, Brown JC, Maher M, Tadros EM.A 16-year-old American Paint Horse gelding was presented for evaluation of weight loss and high serum thyroid hormone concentrations resulting from a functional thyroid adenoma. The horse showed no response to a thyrotropin-releasing hormone (TRH) stimulation test. Clinical signs resolved following surgical removal of the adenoma. . Un cheval American Paint Horse hongre âgé de 16 ans fut présenté pour évaluation à la suite d’une perte de poids et d’une concentration sérique élevée d’hormone thyroïdienne résultant d’un adénome thyroïdien fonctionnel. Le cheval ne démontrai...
Woods GL, Ginther OJ.The efficacy of an equine pituitary extract for induction of multiple ovulations during the ovulatory season was studied in 112 horse mares in four experiments. Combined for all experiments, 70% of the mares (78/112) had multiple ovulations for an average of 3.0 ovulations per mare. The interval between first and last ovulation was decreased (P<0.01) when human chorionic gonadotropin (hCG) was included in the treatment regimen (0.0+/-0.0 versus 1.6+/-0.4 days). Ovulation rate was lower (P<0.01) when extract treatment was initiated at day 19 (1.3+/-0.2) than when initiated at day 15 post-...
Collins SM, Zieba DA, Williams GL.We tested the hypothesis that continuous subcutaneous treatment with low-dose GnRH, administered to mares from late September/early October through March, would prevent the development of seasonal anovulation. Quarter Horse mares (n=20) were stratified by age and body condition score and assigned randomly to either a saline control (n=9) or a GnRH (n=11) treatment group. Gonadotropin-releasing hormone was delivered continuously via osmotic minipumps, with sham pumps placed in control mares. Initial pumps were inserted on Day 3 following ovulation or during the follicular phase if the next anti...
Tan JH, Sasaki F.To determine the effect of age on immunocytochemical staining characteristics of adenohypophyseal cells of Mongolian pony mares and stallions. Methods: 35 Mongolian ponies. Methods: Pituitary glands from 1- to 22-year-old horses of both sexes were collected at a commercial slaughterhouse in China and allocated into 7 groups according to age and sex: prepubertal stallions (n = 5; 1 to 2 years old), young stallions (6; 3 to 7 years old), middle-aged stallions (4; 10 to 12 years old), old stallions (5; 15 to 22 years old), young mares (3; 3 to 7 years old), middle-aged mares (5; 10 to 12 years ol...
KIVALO E, TALANTI S.A good deal of hypothetical evidence has been presented for the view that the antidiuretic and oxytocic hormones are not produced in the posterior lobe of the hypophysis. These hormones appear to originate from a neurosecretory process in the neurosecretory nerve cells of the supraoptic and paraventricular nuclei in the hypothalamus and to migrate within the nerve fibers of the supraoptico-hypophysial tract and into the neurohypophysis (Hild, 1951, 1954 a, b and Hild & Zetler, 1951, 1952, 1953 a, b). Here they are stored and if necessary released. Neurosecretory neurons are described in many s...
Feige K, Eser MW, Geissbühler U, Balestra E, Metzler K.Hirsutism was the most often observed symptom in horses with a pituitary gland tumor and was present in all 13 examined horses. Other symptoms were atrophy of muscles (n = 10), hyperhidrosis (n = 8), polyuria/polydipsia (n = 5), bulging or supraorbital fat (n = 3), polyphagia (n = 2), apathy (n = 2) and seizures (n = 2). Laminitis was the most frequently observed concurrent disease (n = 8). Hyperglycaemia (mean, 9.9 +/- 3.71 mmol/l) in 13 horses and glucosuria (median, 55 [range, 2-55] mmol/l) in 7 horses were the most important laboratory results. The dexamethasone suppression test was positi...
Evans MJ, Mulligan RS, Livesey JH, Donald RA.Perifused equine anterior pituitary cells were used to investigate the relationships between the secretion of ACTH and substances known to either stimulate (corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP)) or inhibit (cortisol) ACTH secretion. The experiments were designed to mimic the hormone milieu present in vivo in the horse, with cortisol (0 or 100 nmol/l) and CRH (0 or 0.02 nmol/l) perifused continuously, and pulses of AVP (10 nmol/l) applied for 5 min at 30-min intervals. In columns perifused with 0.02 nmol CRH/l there was no significant overall effect of 100 nmol...
Hatazoe T, Kawaguchi H, Hobo S, Misumi K.Equine pituitary pars intermedia dysfunction (PPID) generally occurs in older horses showing hirsutism, delayed molting, weight loss, polydipsia, polyuria, laminitis, and reproductive disorders (in broodmares), but there have been no reports on stallions. This report presents a case of a 21-year-old Thoroughbred stallion that developed hirsutism and experienced delayed molting. There were no abnormal findings for semen quality or the stallion's sexual desire. The horse was diagnosed with PPID based on dexamethasone suppression test and plasma levels of adrenocorticotropic hormone. It was then ...
Roser JF, Tarleton M, Belanger JM.Recent studies in our laboratory investigating plasma gonadotrophin concentrations before and after castration indicate that the hypothalamic-pituitary axis is not the original site of dysfunction in stallions with idiopathic infertility. In the present study, fertile, subfertile and infertile stallions were subjected to replacement therapy with oestradiol and testosterone 1 year after castration to investigate hypothalamic-pituitary axis function further. Fertile (n=5), subfertile (n=3) and infertile (n=2) castrated stallions of Light horse breeds, aged 11-23 years, were given either oestradi...
Townsend J, Westcott K, Tortonese DJ.In the horse, pronounced changes in fertility occur annually in response to photoperiod. However, the mechanisms regulating gonadotrophin synthesis and release in this species remain unclear. Here, we investigated the expression of gonadotrophin subunits and GnRH receptor (GnRH-R) mRNA in the pituitary glands of Thoroughbred horses during the breeding (BS) and non-breeding (NBS) season. Seasonal effects on the prevalence of gonadotrophs in the pars distalis were also examined. GnRH-R and common alpha-, LHbeta- and FSHbeta-subunit mRNA contents were determined by Northern analysis and the preva...
Aurich C, Schlote S, Hoppen HO, Klug E, Hoppe H, Aurich JE.To investigate an involvement of endogenous opioids in the regulation of circannual changes in reproductive activity, effects of the opioid antagonist naloxone on the concentration of immunoreactive and bioactive luteinizing hormone (LH) in plasma were measured in mares during the anovulatory season. Naloxone (0.5 mg/kg i.v.) caused a significant increase (P < 0.05) in immunoreactive as well as bioactive LH concentration in plasma. The amplitude of the increase in LH concentrations measured with an in vitro bioassay was more pronounced than the amplitude of the increase in LH secretion dete...
Hobbs KJ, Porter E, Wait C, Dark M, MacKay RJ.Magnetic resonance imaging is increasingly available for evaluation of horses with suspected pituitary adenomas; however, published studies describing the MRI features of normal equine pituitary glands are currently lacking. This retrospective, descriptive, anatomic study describes the MRI appearance and size of presumed normal equine pituitary glands and assesses potential correlations between pituitary size, brain size, and patient weight. These findings serve as a reference for MRI evaluation of the equine pituitary gland. Inclusion criteria consisted of adult horses (2-15 years old), over ...
Eagle RC, Tortonese DJ.Little is known about the neuroendocrine control of fertility in the horse. In this species, unusual features characterize the normal estrous cycle such as a prolonged preovulatory LH surge during the follicular phase and a distinctive FSH surge during the midluteal phase. This study investigated the distribution and hormonal identity of gonadotrophs in the pars distalis (PD) and pars tuberalis (PT) of the equine pituitary gland as possible morphological bases for the referred unusual endocrine characteristics. In addition, the proportion of gonadotrophs in relation to other pituitary cell typ...
Stewart F, Goode JA, Allen WR.A heterologous radioimmunoassay was developed and validated for the measurement of horse GH in plasma. It utilized recombinant-derived bovine GH as the radiolabelled ligand, a guinea-pig anti-porcine GH serum as first antibody and pituitary-derived horse GH as standard. Cross-reactivities were high with all of the pituitary and recombinant-derived GH preparations tested (49-140%) and very low (< 0.3%) with horse FSH, LH and prolactin. A synthetic analogue of GH-releasing factor(1-29) stimulated the expected pattern of GH release in foals. Plasma GH concentrations in foals were low at birth (< ...
Roser JF, Chang YS, Papkoff H, Li CH.A specific and sensitive homologous radioimmunoassay has been developed for equine prolactin, suitable for measuring prolactin concentrations in serum of horses. The sensitivity of the assay ranged from 0.4 to 0.6 ng/ml and the intra- and inter-assay coefficients of variation averaged 6.9 and 15.4%, respectively, for five doses of hormone. Cross-reactivity with other mammalian and nonmammalian prolactins and growth hormones was less than 20 and 0.3%, respectively. Cross-reactivity with equine growth hormone was less than 0.07%. Equine serum and pituitary extracts showed parallel dilution-respo...
Muyan M, Roser JF, Dybdal N, Baldwin DM.The objective of the present study was to determine whether the testicular steroids, i.e., testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and estrone sulfate (E1SO4), play a physiological role in regulating LH release in the male horse by direct actions at the anterior pituitary gland. Enzymatically dispersed anterior pituitary cells from stallions (n = 4) or geldings (n = 3) were cultured for 48 h in alpha-modified Eagle's medium containing 10% steroid-free horse medium. To determine the effects of the steroids on the LH response to GnRH, the cells were incubated f...
Thompson DL, Reville SI, Walker MP, Derrick DJ, Papkoff H.To study the possible role of ovarian androgens in regulation of follicle stimulating hormone (FSH) secretion in the cycling mare, five mature, intact mares were treated with testosterone (20 micrograms/kg of body weight) daily during estrus; five control mares received safflower oil on the same schedule. Mares were teased for estrus and samples of jugular blood were drawn daily through one full estrous cycle. Concentrations of FSH in plasma were measured by a newly developed radioimmunoassay based on anti-ovine FSH serum and radioiodinated equine FSH. Testosterone treatment during estrus had ...
Tortonese DJ, Gregory SJ, Eagle RC, Sneddon CL, Young CL, Townsend J.The intrahypophysial mechanisms involved in the control of gonadotrophin secretion remain unclear. In the horse, a divergent pattern of gonadotrophins is observed at different stages of the reproductive cycle in response to a single secretagogue (gonadotrophin-releasing hormone), and dramatic changes in fertility take place throughout the year in response to photoperiod. This species thus provides a useful model to investigate the regulation of fertility directly at the level of the hypophysis. A series of studies were undertaken to examine the cytological arrangements and heterogeneity of gon...
Brinsko SP, Squires EL, Pickett BW, Nett TM.The objective of this study was to determine if prolonged pulsatile administration of homologous gonadotropin-releasing hormone (GnRH) at therapeutic or 5x therapeutic doses would cause down-regulation of the stallion's hypothalamic-pituitary-testicular axis. Fifteen stallions were randomly assigned to three treatment groups (n=5/group) and received a 0.5 ml subcutaneous dose of saline (group 1), 50 microg GnRH (group 2), or 250 microg GnRH (group 3) every 2 hours for 75 days. Weekly evaluations of follicle stimulating hormone, luteinizing hormone, and testosterone and monthly evaluations of d...
de Graaf-Roelfsema E, Back W, Keizer HA, Stout TA, van der Kolk JH.Serial blood samples were collected from three dwarf Friesian foals to examine their endogenous growth hormone (GH) profiles, and the integrity of the GH-insulin-like growth factor-1 (IGF-1) axis was tested in one of them by examining its responses to the administration of GH-releasing hormone (GHRH) and to 10 days of treatment with recombinant equine GH. The basal serum concentrations of IGF-1 in the three dwarf foals were compared with those in nine age-matched normal foals. All the dwarf foals secreted endogenous GH. Stimulation with 7.0 microg/kg GHRH led to a 1400 per cent increase in pla...
Rathnam P, Fujiki Y, Landefeld TD, Saxena BB.Six hundred milligrams of follicle-stimulating hormone (FSH), containing 110 NIH-FSH-S1 units/mg, was isolated from 9 kg of equine pituitary glands. The equine FSH was dissociated into alpha- and beta-subunits. A tentative amino acid sequence of the alpha-subunit was determined. The alpha-subunit contained 82 amino acids. The equine FSH-alpha is shorter by 10 to 14 amino acids at the NH2 terminus and has several substitutions at several positions as compared with human FSH-alpha and bovine thyroid-stimulating hormone-alpha. At the intraspecies level, the alpha-subunits of human FSH, human lute...
Watson ED, Heald M, Tsigos A, Leask R, Steele M, Groome NP, Riley SC.Ten mares were studied from February (winter anoestrus) to their second ovulation in the breeding season to investigate the relationship between resumption of ovarian cyclicity in the spring and circulating concentrations of FSH, inhibin A and inhibin isoforms containing pro- and -alphaC immunoreactivity. An additional four mares were studied during one oestrous cycle. Growth and regression of ovarian follicles were monitored by transrectal ultrasonography. The frequency of blood sampling varied from three times a week to once a day, depending on the follicular activity present. Concentrations...
Baldwin DM, Roser JF, Muyan M, Lasley B, Dybdal N.Enzymatically dispersed anterior pituitary cells from donor mares were cultured for 48 h in alpha-modified Eagles' medium containing 10% steroid-free horse serum. The cells were then incubated for 24 h in fresh medium oestrogen followed by a 4-h incubation with or without GnRH. Media and cell extracts were analyzed for LH by radioimmunoassay. In the first series of experiments, pituitary cells from Day-3 dioestrous mares were preincubated with ethanol (control) or different concentrations of E2 (10(-11) to 10(-7) M) for 24 h prior to a 4-h incubation without (basal) or with 1.0 nM GnRH. E2 inc...
Timms M, Ganio K, Forbes G, Bailey S, Steel R.CJC-1295 is a 30 amino acid peptide-based drug that stimulates the release of growth hormone (GH) from the pituitary gland. It is unique among performance-enhancing peptides due to the presence of a reactive maleimidopropionic acid group that covalently links the peptide to free thiols on the surface of plasma proteins. Once conjugated, CJC-1295 remains active in the bloodstream for significantly longer than non-conjugated peptide-based drugs that are rapidly excreted. Conjugation of CJC-1295 to plasma proteins prevents its detection by top-down mass-spectrometry-based peptide screening protoc...
Perillo A, Passantino G, Passantino L, Cianciotta A, Mastrosimini AM, Lacovazzi P, Venezia P, Jirillo E, Troncone A.Among 622 slaughtered horses from eastern Europe, 156 thyroid glands were selected on the basis of macroscopic alterations (e.g., determination of volume and weight). In the 80% of these thyroids, microscopic alterations consistent with a diagnosis of Hashimoto thyroiditis-like disease were found. In particular, a subverted architecture of the thyroid gland with colloid rarefaction, lymphocytic infiltration, and fibrosis was noted. The confirmation of the histopathological diagnosis of an equine Hashimoto thyroiditis-like disease was provided by the increased serum concentration of thyroglobul...
Irvine CH, Alexander SL.Pituitary venous blood was collected by a painless nonsurgical cannulation method from five ambulatory stallions at 5-min intervals for 5-6 h during the breeding season. In four adult stallions, statistical analysis showed that pulses of gonadotrophin-releasing hormone (GnRH) and LH were coincident (P less than 0.01), as were pulses of FSH and LH (P less than 0.05). Furthermore, the patterns of changes in concentration of FSH and LH were highly correlated in each of the four stallions. However, seemingly ineffective pulses of GnRH were also observed, with 28% of GnRH pulses failing to induce a...
Irvine CH, Alexander S.Serum LH was measured by radioimmunoassay in 5 long-term (greater than or equal to 3 years) castrated male horses bled at 30-min intervals for 2 h twice a month from March to February. There was no significant effect of month on LH levels; however, mean levels were significantly lower in spring than autumn (P less than 0.05). By contrast, stallions in the same environment showed a markedly seasonal pattern of LH secretion, with LH rising at the onset of the breeding season to reach levels in late spring 3-4 times those in early winter. Despite differences in seasonal patterns of secretion, ann...
