Functional heterogeneity of corticotrophs in the anterior pituitary of the sheep fetus

Abstract

1. Parturition in the sheep is dependent on prepartum stimulation of the hypothalamo-pituitary-adrenal axis and an increase in fetal plasma cortisol concentration. We have investigated whether there are changes in the functional 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 ml 24 h-1 i.v.; n = 10) between 109 and 116 days gestation and pituitary glands were collected from these two groups, and from a late gestational group (140-145 days gestation; n = 10) for cell culture. Cells in half the wells from each pituitary were treated with cytotoxin (Cx; a cytotoxic analogue of corticotrophin releasing hormone (CRH)) to eliminate CRH target cells before exposure to ovine (o)CRH (10-8 M), arginine vasopressin (AVP; 10-7 M) or oCRH + AVP. 3. We have demonstrated that around 70 % of adrenocorticotrophic hormone (ACTH) in the fetal anterior pituitary is stored within corticotrophs which are 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 before delivery.

Figure 1. Effect of cytotoxin on ACTH secretion

The proportion (means +s.e.m.) of total ACTH secreted during basal conditions in the three treatment groups (116d + Sal, n = 10; 116d + F, n = 11; 140-145d, n = 10) in the absence (□) and presence (▪) of the CRH-cytotoxin conjugate. The asterisks indicate significant differences between the percentage of ACTH secreted in the absence and presence of Cx in each treatment group.

Figure 2. Proportion of ACTH in CRH-responsive cells

The proportion (means +s.e.m.) of ACTH present in CRH-responsive cells in each of the three treatment groups. The asterisk indicates that the proportion of ACTH present in the CRH-responsive cells was significantly lower in the 116d + F group (n = 11) than in either the 116d + Sal (n = 10) or 140-145d (n = 10) groups.