The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep

There is a sex difference in the hypothalamo-pituitary-adrenal (HPA) axis o f many species, although there are sparse data on the sheep. In the present study we have compared the HPA axes of intact and gonadectomised adult mal e and female sheep at the level of the median eminence, pituitary and adren al glands using a variety of in vitro approaches. The concentration of argi nine vasopressin (AVP) was higher (P<0.01) in the median eminence of male t han female sheep, and was also elevated by gonadectomy of either sex (P<0.0 1). The concentration of corticotrophin-releasing factor (CRF) in the media n eminence did not differ between the sexes, but was also elevated in both sexes following gonadectomy (P<0.01). Anterior pituitary pro-opiomelanocort in mRNA concentrations were higher (P<0.05) in intact male sheep than in in tact females, with the levels in gonadectomised animals of both sexes being intermediate. In contrast to this finding, basal ACTH secretion from anter ior pituitary cells was higher (P<0.05) in cultures derived from female she ep than those from males, but gonadectomy was without effect. There was no effect of sex or gonadectomy on in vitro ACTH secretion in response to AVP, CRF or the combination of AVP and CRF, and in all cases the combination of AVP and CRF generated greater (P<0.0001) ACTH secretion than AVP :done. AV P alone was more effective (P<0.01) than CRF alone as an ACTH secretagogue. The adrenal glands were larger (P<0.05) in female than male sheep, with no effect of gonadectomy. Basal cortisol production was greatest (P<0.05) in cultures of adrenal cells from intact male sheep, though ACTH- and 8BrcAMP- induced cortisol production was greater in the cultures of cells from femal es (P=0.05); there were no effects of gonadectomy. Cultures of adrenocortic al cells front male sheep had greater (P<0.05) basal cAMP production, but A CTH-stimulated cAMP production did not differ between any of the groups of animals. These finding; show a range of differences in the HPA axis of male and female sheep. Furthermore, they suggest that the heightened activity o f the axis in the female occurs primarily due to differences at the level o f the adrenal gland, and that greater adrenal responsiveness of female anim als is due to differences in the latter stages of steroidogenesis, rather t han an effect on ACTH signal transduction at its receptor.