English
French
Endocrinology.
Publisher:
Association for the Study of Internal Secretions,. New York : Oxford University Press (2017)
Frequency: Monthly
Country: United States
Language: English
Author(s):
Association for the Study of Internal Secretions (U.S.), Endocrine Society.
Start Year:1917 -
ISSN:
0013-7227 (Print)
1945-7170 (Electronic)
0013-7227 (Linking)
1945-7170 (Electronic)
0013-7227 (Linking)
Impact Factor
4.8
2022
| NLM ID: | 0375040 |
| (DNLM): | E07180000(s) |
| (OCoLC): | 01567879 |
| Coden: | ENDOAO |
| LCCN: | sg 39000030 |
| Classification: | W1 EN396S |
Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia Dysfunction. Equine Cushing disease [pituitary pars intermedia dysfunction (PPID)] is a common condition of older horses, but its pathophysiology is complex and poorly understood. In contrast to pituitary-dependent hyperadrenocorticism in other species, PPID is characterized by elevated plasma ACTH but not elevated plasma cortisol. In this study, we address this paradox and the hypothesis that PPID is a syndrome of ACTH excess in which there is dysregulation of peripheral glucocorticoid metabolism and binding. In 14 horses with PPID compared with 15 healthy controls, we show that in plasma, cortisol levels...
Nodal Promotes Functional Luteolysis via Down-Regulation of Progesterone and Prostaglandins E2 and Promotion of PGF2α Synthetic Pathways in Mare Corpus Luteum. In the present work, we investigated the role of Nodal, an embryonic morphogen from the TGFβ superfamily in corpus luteum (CL) secretory activity using cells isolated from equine CL as a model. Expression pattern of Nodal and its receptors activin receptor A type IIB (ACVR2B), activin receptor-like kinase (Alk)-7, and Alk4, as well as the Nodal physiological role, demonstrate the involvement of this pathway in functional luteolysis. Nodal and its receptors were immune localized in small and large luteal cells and endothelial cells, except ACVR2B, which was not detected in the endothelium. Nod...
The absence of ER-β results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles. Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER)-β is highly expressed in ovarian granulosa cells, and mice lacking ER-β are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and, although informative, provides confounding results due to the heterogeneous cell types present including granulosa and theca cells and oocytes and exposure to in...
Biological and anatomical evidence for kisspeptin regulation of the hypothalamic-pituitary-gonadal axis of estrous horse mares. The purpose of the present study was to evaluate the effects of kisspeptin (KiSS) on LH and FSH secretion in the seasonally estrous mare and to examine the distribution and connectivity of GnRH and KiSS neurons in the equine preoptic area (POA) and hypothalamus. The diestrous mare has a threshold serum gonadotropin response to iv rodent KiSS decapeptide (rKP-10) administration between 1.0 and 500 microg. Administration of 500 microg and 1.0 mg rKP-10 elicited peak, mean, and area under the curve LH and FSH responses indistinguishable to that of 25 microg GnRH iv, although a single iv injection...
Quantifying nonlinear interactions within the hypothalamo-pituitary-adrenal axis in the conscious horse. Cortisol is an important mediator of physiological stress responses. Hypothalamic CRH and arginine vasopressin (AVP) and pituitary ACTH, in addition to hypothalamic and pituitary cortisol feedback, regulate cortisol secretion. Importantly, joint interactions among the four, rather than the signal of any one hormone, govern this life-preserving axis. Quantifying in vivo strength of such joint interactions has been difficult, especially without direct injection of cortisol, CRH, AVP, or ACTH. The goal of the present research was to estimate these joint feedback and feedforward interactions in vi...
The cloned equine thyrotropin receptor is hypersensitive to human chorionic gonadotropin; identification of three residues in the extracellular domain involved in ligand specificity. The receptors for TSH, LH/chorionic gonadotropin (CG), and FSH belong to the same subfamily of G protein-coupled receptors. The specificity of recognition of their cognate hormone involves a limited number of residues in the leucine-rich repeats present in the N-terminal ectodomain of the receptor. It is admitted that receptors of this subfamily coevoluted with their respective ligands. The secretion of CG is restricted to gestation of primates and Equidae. We hypothesized that, facing the challenge of a new hormone, the glycoprotein hormone receptors would have evolved differently in Equidae ...
The adrenocorticotropin stimulation test: contribution of a physiologically based model developed in horse for its interpretation in different pathophysiological situations encountered in man. The present study aimed to characterize the adrenal response to ACTH. A model was developed that coupled the nonlinear disposition of cortisol with a physiologically based model for cortisol secretion by the adrenals. It was assumed that the response to ACTH resulted from two mechanisms: a stimulation of the cortisol secretion rate and control of the duration of the secretion. Seven dose levels of ACTH were tested in horses, a species similar to man as regards adrenal function. The main result was that the secretion rate of the adrenal gland can be modelized by a zero order process that is max...
Human chorionic gonadotropin-dependent regulation of 17beta-hydroxysteroid dehydrogenase type 4 in preovulatory follicles and its potential role in follicular luteinization. 17Beta-hydroxysteroid dehydrogenase type 4 (17betaHSD4) has a unique multidomain structure, with one domain involved in 17beta-estradiol inactivation. The objective of the study was to investigate the regulation of 17betaHSD4 during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine 17betaHSD4 cDNA was cloned and was shown to encode a 735-amino acid protein that is highly conserved (81-87% identity) compared with other mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of 17betaHSD4 transcripts in equine preovulatory follicles ...
Induction of hyaluronan synthase 2 by human chorionic gonadotropin in mural granulosa cells of equine preovulatory follicles. In contrast to other species, the preovulatory rise in gonadotropins in mares causes a remarkable expansion of the entire granulosa cell layer in vivo, suggesting that hyaluronan (HA) synthesis may be regulated in mural granulosa cells in this species. The objectives of this study were to clone and characterize equine hyaluronan synthase 2 (HAS2) and investigate the regulation of its transcript and of HA synthesis in equine follicles during human chorionic gonadotropin (hCG)- induced ovulation. Results showed that the equine HAS2 cDNA contains a 5'-untranslated region of 436 bp, an open readin...
Pregnancy-associated plasma protein-A (PAPP-A) in ovine, bovine, porcine, and equine ovarian follicles: involvement in IGF binding protein-4 proteolytic degradation and mRNA expression during follicular development. IGF binding protein-4 (IGFBP-4) proteolytic degradation is a common feature of preovulatory follicles from human, ovine, bovine, porcine, and equine ovary. In all these species, the protease is a zinc-dependent metalloprotease and its ability to degrade IGFBP-4 is IGF dependent. The human intrafollicular IGFBP-4-degrading protease has recently been identified as pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to investigate whether PAPP-A is also involved in IGFBP-4 degradation in ovine, bovine, porcine, and equine preovulatory follicles and to study the expression of...
Expression and regulation of transcripts encoding two members of the NR5A nuclear receptor subfamily of orphan nuclear receptors, steroidogenic factor-1 and NR5A2, in equine ovarian cells during the ovulatory process. Steroidogenic factor-1 (SF-1, NR5A1a) is a member of the NR5A nuclear receptor subfamily and has been implicated as a key transcriptional regulator of all ovarian steroidogenic genes in vitro. To establish links between the expression of SF-1 and that of the steroidogenic genes in vivo, the objectives of this study were to clone equine SF-1 and examine the regulation of its messenger RNA (mRNA) in follicular cells during human CG (hCG)-induced ovulation. The equine SF-1 primary transcript was cloned by a combination of RT-PCR techniques. Results showed that the transcript was composed of a 5'-...
Dual regulation of promoter II- and promoter 1f-derived cytochrome P450 aromatase transcripts in equine granulosa cells during human chorionic gonadotropin-induced ovulation: a novel model for the study of aromatase promoter switching. Estradiol biosynthesis is a key biochemical trait of developing follicles. To study its regulation in equine follicles, the objectives of this study were to clone and determine the structure of equine cytochrome P450 aromatase (P450AROM), and characterize the regulation of P450AROM and P450 17alpha-hydroxylase/C17-20 lyase (P45017alpha) messenger RNAs (mRNAs) in vivo in equine preovulatory follicles isolated during hCG-induced ovulation. Two distinct P450AROM complementary DNAs (cDNAs) were isolated from an equine preovulatory follicle cDNA library. One clone was 2682 bp in length and included...
Hepatocyte growth factor induces rat ovarian surface epithelial cell mitosis or apoptosis depending on the presence or absence of an extracellular matrix. The present studies showed that sequential treatment with equine CG (eCG) and hCG not only induced an increase in ovarian weight, but also caused an estimated 4.6-fold increase in the number of ovarian surface epithelial cells. In addition, eCG-hCG treatment increased ovarian hepatocyte growth factor (HGF) messenger RNA levels. These studies also demonstrated that rat primary ovarian surface epithelial cells as well as a cell line derived from rat ovarian surface epithelium (i.e. ROSE-179 cells) do not express the LH (hCG) receptor. Both of these cells express c-Met, the receptor for HGF. To a...
Human chorionic gonadotropin induces an inverse regulation of steroidogenic acute regulatory protein messenger ribonucleic acid in theca interna and granulosa cells of equine preovulatory follicles. The time- and gonadotropin-dependent regulation of steroidogenic acute regulatory protein (StAR) has not been characterized in vivo in preovulatory follicles of large monoovulatory species or sexually mature animals. The objectives of this study were to clone equine StAR and describe the regulation of its messenger RNA (mRNA) in equine follicles after the administration of an ovulatory dose of hCG. The screening of an equine follicle complementary DNA (cDNA) library with a mouse StAR cDNA probe revealed two forms of equine StAR that differ only in the length of their 3'-untranslated region (3'...
The effect of naloxone administration on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin in unperturbed horses. 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...
The acute effect of lowering plasma cortisol on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin as revealed by intensive sampling of pituitary venous blood in the normal horse. The effect of an acute fall in plasma cortisol on the secretion of CRH, arginine vasopressin (AVP), and ACTH was studied using our nonsurgical technique for collecting pituitary venous (PV) blood from horses. PV blood from six mares was collected continuously and divided into 30-sec segments for 0.5 h before and during a 3-h infusion of metyrapone, an 11-beta-hydroxylase inhibitor. During treatment, plasma cortisol fell (P < 0.01) to a mean nadir of 15% of pretreatment levels, and 11-deoxy-cortisol rose (P < 0.02). Three mares became mildly agitated during treatment. Mean PV concentratio...
Secretory patterns and rates of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone revealed by intensive sampling of pituitary venous blood in the luteal phase mare. We used our unique nonsurgical technique for collecting pituitary venous (pit) blood to study GnRH, FSH, and LH secretion patterns in midluteal phase mares. This method does not perturb endocrine function and allows continuous monitoring of GnRH and gonadotropin (Gn) secretion, determination of the amount of GnRH perfusing gonadotropes, and direct measurements of the amounts of Gn secreted. In a total of 80 h of 5-min sampling in four mares, eight Gn peaks occurred; however, more frequent sampling was needed to define secretory events precisely. Therefore, pit blood was collected continuously ...
Immunochemical studies of equine chorionic gonadotropin (eCG), eCG alpha, and eCG beta. The equine (e) placental glycoprotein hormone eCG plays a critical though not completely understood role during the first trimester of gestation in mares. In the present work, we have developed immunoradiometric assays (m-IRMAs) for detection of eCG, eCG alpha, and eCG beta using combinations of monoclonal antibodies (mAbs) specific for epitopes that reside on free and/or combined subunits. The free eCG alpha m-IRMA was based on AHT20 mAb, specific for the free alpha-subunit of all species, and 125I-labeled ECG01 mAb, which recognizes both free and combined alpha-subunit from equine and primat...
Reduction and reoxidation of equine gonadotropin alpha-subunits. Ovine (o) and equine (e) LH alpha-subunits were reduced and reoxidized using conditions known to be effective for bovine and human alpha-subunits. The major product of oLH alpha refolding was alpha-subunit monomer. In contrast, eLH alpha formed a 121,000 mol wt aggregate. Monomeric eLH alpha was recovered, but in greatly reduced yield. To test the effects of carbohydrate variation on the aggregation of equine alpha-subunits, all of the equine gonadotropin alpha-subunits (eFSH alpha, eCG alpha, eLH alpha, and free alpha-subunit) were reduced and reoxidized. In each case, the major product was t...
Gonadotropin-induced up- and down-regulation of ovarian follicle-stimulating hormone (FSH) receptor gene expression in immature rats: effects of pregnant mare’s serum gonadotropin, human chorionic gonadotropin, and recombinant FSH. The actions of gonadotropins on ovarian differentiation are associated with dynamic changes in gonadotropin receptor content, presumably due to modulation of receptor gene expression. The present studies used a reverse transcription-polymerase chain reaction to obtain a rat FSH receptor cDNA fragment, followed by synthesis of a labeled cRNA probe to examine the regulation of FSH receptor mRNA levels during follicular maturation, ovulation, and luteinization. Northern blot analysis of ovarian RNA with the FSH receptor probe revealed two predominant hybridization signals of 7.0 and 2.5 kilobases...
Affinity purification and sequence determination of equine relaxin. Relaxin, a polypeptide hormone normally associated with pregnancy, has been purified from many species, and the sequence determined for a growing number. Equine relaxin has been previously purified by acetone extraction, gel filtration, and ion exchange chromatographies. In an attempt to develop a more rapid and efficient method for relaxin purification, the use of affinity chromatography coupled with HPLC was explored. Monoclonal antibodies were raised against highly purified equine relaxin; large quantities of antibody were obtained by ascites production and attached to a solid phase support...
Circulating antagonist of luteinizing hormone in association with infertility in stallions. Using a LH radioligand receptor assay (RRA) previously validated for use in serum and an equine monoclonal RIA, we have distinguished a subset of subfertile stallions with an elevated RRA/RIA ratio. After purification of the active moiety by anion exchange chromatography and immunoprecipitation with the equine LH (eLH) monoclonal antibody, RRA activity remained in the supernatant. This activity was also recognized by a polyclonal LH antibody (GDN 15) with wide cross-species recognition. This active fraction was further purified by gel filtration chromatography and shown to displace labeled eLH...
Steroidogenesis by equine preovulatory follicles: relative roles of theca interna and granulosa cells. Estrous cycles in mares have several unique characteristics, including the presence of a long period of estrus and the absence of a typical LH surge. Like follicles of other species, equine preovulatory follicles are characterized by their ability to secrete large amounts of 17 beta-estradiol, but it is not clear which follicular cell type is responsible for estradiol synthesis in mares. To better understand the relative roles of theca interna and granulosa cells in follicular steroidogenesis, presumptive ovulatory follicles were obtained from mares during early estrus (first or second day of ...
The effect of acute exercise on the secretion of corticotropin-releasing factor, arginine vasopressin, and adrenocorticotropin as measured in pituitary venous blood from the horse. We have used the technique which we have developed for collecting pituitary venous blood from conscious, undisturbed horses to study the effect of acute vigorous exercise on the secretion of CRF, arginine vasopressin (AVP) and ACTH. Pituitary venous (pit) blood was collected every 1-5 min from nine trained racehorses at rest in the stable. The horses then trotted quietly for 10 min, after which they galloped as fast as possible for 4-6 min, before returning to the stable where sampling continued. In Exp 1 (n = 5) no blood samples were taken during exercise, whereas in Exp 2 (n = 4), pit blood ...
Developmental changes in steroidogenesis by equine preovulatory follicles: effects of equine LH, FSH, and CG. Ovulation in mares is preceded by a long and variable estrous period. The differentiation of equine preovulatory follicles with respect to steroidogenic capacity and responsiveness to equine gonadotropins was studied by culturing pieces of follicle wall (FW = theca + attached granulosa cells) from preovulatory follicles isolated during late diestrus (day 14 of cycle, n = 5 mares), early estrus (1st-2nd day of estrus, n = 6) or late estrus (4th or 5th day of estrus, n = 6). FW was cultured with or without equine LH, FSH, LH + FSH, or CG (10 or 100 ng/ml) and medium was collected and replaced at...
Effect of an osmotic stimulus on the secretion of arginine vasopressin and adrenocorticotropin in the horse. Arginine vasopressin (AVP) is released in response to changes in blood osmolality and is also a putative secretagogue for ACTH. However, it is unclear whether osmotically generated increases in AVP in the physiological range influence ACTH secretion. We have studied this question using our unique noninvasive technique for collecting pituitary venous blood in six normal conscious horses that received an iv infusion of hypertonic saline (HS; 5%, 0.07 ml/kg.min) for 45-60 min. Pituitary and jugular venous samples were collected every 5 min for 40 min before, during, and for 20 min after HS. Durin...
Equine Cushing’s disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary. Equine Cushing's disease is caused by an adenomatous hyperplasia of the intermediate pituitary which secretes high levels of beta-endorphin, ACTH, and other peptide derivatives of POMC. In the present study we found that plasma and cerebrospinal fluid immunoreactive beta-endorphin (i beta-endorphin) levels were 60- and 120-fold higher than control values in horses with Cushing's disease. There were no significant differences in intermediate lobe i beta-endorphin concentrations, although anterior lobe i beta-endorphin was significantly reduced in Cushing's horses, presumably because high levels...
The effects of cortisol, vasopressin (AVP), and corticotropin-releasing factor administration on pulsatile adrenocorticotropin, alpha-melanocyte-stimulating hormone, and AVP secretion in the pituitary venous effluent of the horse. Plasma ACTH, arginine vasopressin (AVP), and alpha MSH were measured in pituitary venous effluent at 5-min intervals from five unanesthetized horses during cortisol infusion and after an iv bolus of AVP or ovine (o) CRF. In control experiments (no hormone) there was a significant overall correlation between the timing of concentration changes in ACTH and alpha MSH. Cortisol infusion increased jugular cortisol levels by 70% and was associated with a reduction in mean ACTH, AVP, and alpha MSH secretion rates and ACTH peak secretion rate, but did not alter the observed pulse frequencies of these ...
Development of a homologous equine relaxin radioimmunoassay. Equine relaxin (eRlx) immunoactivity has previously been measured in the mare during pregnancy using the porcine relaxin (pRlx) RIA (pRlx-RIA). This was not the optimal system for measurement of eRlx because the dose-response curve obtained with equine plasma was not parallel to the pRlx standard curve. A homologous eRlx-RIA has been developed and used to measure relaxin immunoactivity during pregnancy and parturition in the mare. Highly purified eRlx was used for the generation of antiserum in rabbits, preparation of tracer, and as assay standards. A double antibody eRlx RIA (eRlx-RIA) was de...
Purification and characterization of equine relaxin. It has been previously determined that the equine placenta is the sole significant source of relaxin during pregnancy and that relaxin immunoactivity is also present in term placentas. Therefore, placentas obtained at the time of foaling were selected for starting material for purification of equine relaxin. Frozen whole placentas were ground and then extracted with 0.5 N HCl-85% acetone. Relaxin was precipitated by raising the acetone concentration to 97%. Equine relaxin was further purified by stepwise elution ion exchange, gel filtration, and gradient elution ion exchange chromatographies a...
