Foetal endocrine maturation.

The research focuses on the process of foetal endocrine maturation in domestic ruminant animals, with a particular emphasis on sheep. It explores how the hypothalamic-pituitary-adrenal (HPA) axis matures and influences the increased production of cortisol, an essential hormone for birth. The study further investigated certain factors which regulate foetal pituitary adrenocorticotrophin (ACTH) secretion and noted how cortisol manipulates its own mechanism for promoting foetal adrenal function.

Role and Regulation of Adrenocorticotrophin (ACTH)

• The study first delineates the regulating factors of foetal pituitary adrenocorticotrophin secretion. These include corticotrophin releasing hormone (CRH), arginine vasopressin, prostaglandin (PG) E2 and endogenous opioids.
• The increase of ACTH in the foetal plasma before birth results in higher levels of pro-opiomelanocortin (POMC) mRNA and an altered pattern of POMC after it has been translated into protein.
• ACTH receptor numbers increase and its coupling through the Gs protein to adenylate cyclase is enhanced, resulting in foetal adrenal activation. Expression of key steroidogenic enzymes including P450c17 also increases.

Role of Cortisol in Foetal Adrenal Function

• Cortisol adjusts the mechanism by which ACTH modulates foetal adrenal function via specific glucocorticoid receptors in the foetal adrenal cortex.
• Even though the numbers of GR change throughout the pregnancy, the overall abundance of GR mRNA remains stable, implying there are post-translational regulatory mechanisms involved.
• Cortisol also causes an increase in its own high-affinity binding protein (corticosteroid binding globulin; CBG) in the foetal circulation, which could be due to increased CBG gene expression in the foetal liver, and modified extent of foetal CBG glycosylation — a change that would likely decrease the metabolic clearance of this glycoprotein.

Potential Role of the Placenta

• There is still no definitive evidence that placentally-produced CRH and ACTH exist in sheep. However, research suggests that prostaglandin E2 (PGE2), which is produced in increasing amounts by the placenta during late gestation, might increase the maturation of the HPA axis.

Comparison with Other Species

• Elements of the cortisol biosynthesis pathway’s maturation have been described in other species, including horses. This research compares those findings with the more detailed information available from ruminants such as sheep.