Functional heterogeneity of corticotrophs in the anterior pituitary of thesheep fetus

1. Parturition in the sheep is dependent on prepartum stimulation of the hy pothalamo pituitary-adrenal axis and an increase in fetal plasma cortisol c oncentration. We have investigated whether there are changes in the functio nal characteristics of the corticotrophic cells in the week before delivery or in response to an increase in circulating cortisol. 2. Fetal sheep were infused with cortisol(2-3 mg 24 h(-1) I.v.; n = 11), or saline (4.4 mi 24 h(-1) I.v.; n = 10) between 109 and 116 days gestation a nd pituitary glands were collected from these two groups, and from a late g estational group (140-145 days gestation; n = 10) for cell culture. Cells i n half the wells from each pituitary were treated with cytotoxin (Cx; a cyt otoxic analogue of corticotrophin releasing hormone (CRH)) to eliminate CRH target cells before exposure to ovine (o)CRH (10(-8) M), arginine vasopres sin(AVP; 10(-7) ar) or oCRH + AVP. 3. We have demonstrated that around 70% of adrenocorticotrophic hormone (AC TH) in the fetal anterior pituitary is stored within corticotrophs which ar e CRH responsive. Cortisol acts to inhibit ACTH synthesis in corticotrophic cells which are CRH responsive, whereas AVP-responsive cells in the fetal pituitary are relatively resistant to cortisol. 4. We propose that the stimulatory influence of the fetal hypothalamus must counteract the negative feedback effect of cortisol in the CRH-responsive cells to stimulate the increase in pituitary ACTH output which occurs befor e delivery.