Foetal endocrine maturation.
In domestic ruminants such as the sheep, birth is effected through sequential maturation of the foetal hypothalamic-pituitary-adrenal (HPA) axis, leading to the increased output of cortisol. Factors regulating foetal pituitary adrenocorticotrophin (ACTH) secretion have been delineated, and these include corticotrophin releasing hormone (CRH), arginine vasopressin, prostaglandin (PG) E2 and endogenous opioids. The pre-partum increase in foetal plasma ACTH is associated with a rise in pro-opiomelanocortin (POMC) mRNA in the foetal pars distalis, and with an altered pattern of POMC post-translational processing. Foetal adrenal activation results from an increase in ACTH receptors and enhanced coupling through the Gs protein to adenylate cyclase, and increased expression of key steroidogenic enzymes including P450c17. Cortisol modulates the mechanism by which ACTH activates foetal adrenal function, through specific glucocorticoid receptors (GR) in the foetal adrenal cortex. Although the numbers of GR change with gestation, the relative abundance of GR mRNA does not, pointing to post-translational regulatory mechanisms. Cortisol also stimulates an increase in the concentration of its own high affinity binding protein (corticosteroid binding globulin; CBG) in the foetal circulation, apparently by increasing CBG gene expression in the foetal liver, and by altering the extent of foetal CBG glycosylation in a manner that would be expected to decrease the metabolic clearance of this glycoprotein. Clear evidence for placental CRH and ACTH production is lacking in sheep, but PGE2, produced in increasing amounts by the placenta during late pregnancy, may augment the drive to HPA maturation. Aspects of the maturational pathway of cortisol biosynthesis have been described in other species, including the horse, and some comparison is made with the more detailed information currently available from species such as the sheep.
Challis
J R
JR
Lawson Research Institute, St. Joseph's Health Centre, Department of Obstetrics and Gynaecology, University of Western Ontario, London, Canada.
Bassett
N
N
Berdusco
E T
ET
Han
V K
VK
Lu
F
F
Riley
S C
SC
Yang
K
K
D000818:Animals; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology* / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000196:embryology* / Q000502:physiology; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D012756:Sheep / Q000196:embryology* / Q000502:physiology; D014156:Transcortin / Q000502:physiology
D014156:Transcortin