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

Abstract

There is a sex difference in the hypothalamo-pituitaryadrenal (HPA) axis of 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 male and female sheep at the level of the median eminence, pituitary and adrenal glands using a variety of in vitro approaches. The concentration of arginine vasopressin (AVP) was higher (P<0·01) in the median eminence of male than female sheep, and was also elevated by gonadectomy of either sex (P<0·01). The concentration of corticotrophin-releasing factor (CRF) in the median eminence did not differ between the sexes, but was also elevated in both sexes following gonadectomy (P<0·01). Anterior pituitary pro-opiomelanocortin mRNA concentrations were higher (P<0·05) in intact male sheep than in intact females, with the levels in gonadectomised animals of both sexes being intermediate. In contrast to this finding, basal ACTH secretion from anterior pituitary cells was higher (P<0·05) in cultures derived from female sheep 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 alone. AVP 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 females (P=0·05); there were no effects of gonadectomy. Cultures of adrenocortical cells from male sheep had greater (P<0·05) basal cAMP production, but ACTH-stimulated cAMP production did not differ between any of the groups of animals. These findings show a range of differences in the HPA axis of male and female sheep. Furthermore, they suggest that the heightened activity of the axis in the female occurs primarily due to differences at the level of the adrenal gland, and that greater adrenal responsiveness of female animals is due to differences in the latter stages of steroidogenesis, rather than an effect on ACTH signal transduction at its receptor.

Suppression of the secretion of luteinizing hormone due to isolation/restraint stress in gonadectomised rams and ewes is influenced by sex steroids

“…In this experiment, however, there were no differences between gonadectomised rams and ewes, or between gonadectomised sheep given different sex-steroid treatments, in either the basal or stress-induced concentrations of cortisol. Although there is some evidence that sex and gonadal factors may play a role in modulating the response of the hypothalamo-pituitary-adrenal axis to a variety of stimuli in sheep in vivo (Cook 1997(Cook , 1998 and in vitro (Canny et al 1999), the current study specifically compared the effects of physiologically relevant concentrations of androgens, oestrogens and progesterone on the activity of the hypothalamo-pituitary-adrenal axis in gonadectomised sheep. The lack of a sex difference and the lack of effect of the sex steroids on the activity of the hypothalamo-pituitary-adrenal axis in gonadectomised sheep differs from observations in rats where there are clear sex differences and where it has been proposed that oestrogens enhance while androgens depress the activity of the hypothalamo-pituitary-adrenal axis (see Handa et al 1994, Da Silva 1995, Young 1995, Patchev & Almeida 1998.…”

Sex Differences and the Role of Sex Steroids in Sympatho-Adrenal Medullary System and Hypothalamo-Pituitary Adrenal Axis Responses to Stress

“…We have not directly addressed the effects of steroids on the sympatho-adrenal medullary system in sheep but have considered sex differences and the importance of the gonads when it comes to the hypothalamo-pituitary adrenal axis. In adult sheep we identified a range of differences between males and females in the hypothalamo-pituitary adrenal axis and some, but not all, of these differences depended on gonadal factors [99]. Of significance in this study was an enhanced adrenocortical response to ACTH in females compared to males, and this occurred irrespective of the presence or absence of gonads.…”

“…Of significance in this study was an enhanced adrenocortical response to ACTH in females compared to males, and this occurred irrespective of the presence or absence of gonads. Males had higher AVP in the median eminence than females and gonadectomy increased this in both sexes [99].…”

“…In lambs, we found that females had a significantly higher cortisol response to tail docking compared to males and that this sex difference developed between one and eight weeks of age [64]. We have also investigated the mechanisms for sex differences in hypothalamo-pituitary adrenal axis responses to stress and have found various differences between males and females at each level of the axis, some of which depend on gonadal factors [65,66], which are discussed in the next section. These include differences in neuropeptide distribution in the paraventricular nucleus of the hypothalamus [66] as well as adrenal size and adrenal responsiveness to ACTH [65].…”

“…We have also investigated the mechanisms for sex differences in hypothalamo-pituitary adrenal axis responses to stress and have found various differences between males and females at each level of the axis, some of which depend on gonadal factors [65,66], which are discussed in the next section. These include differences in neuropeptide distribution in the paraventricular nucleus of the hypothalamus [66] as well as adrenal size and adrenal responsiveness to ACTH [65]. In humans, there is also evidence that hypothalamo-pituitary adrenal axis responses to stress differ between adult men and women (see [49] for an extensive review of the literature).…”