Effects of sex hormones on the steroidogenic activity of dispersed adrenocortical cells of the rat adrenal cortex

Nowak, Krzysztof W.; Neri, Giuliano; Nussdorfer, Gastone G.; Malendowicz, Ludwik K.

doi:10.1016/0024-3205(95)02015-b

Cited by 56 publications

(42 citation statements)

References 17 publications

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“…Stalvey (2002) similarly demonstrated a reduction by testosterone of 3bHSD activity, immunoreactivity, and m-RNA in cultured mouse adrenal cells under both basal and stimulated conditions. The restriction of the effects of testosterone in the current results to (ACTH) stimulated rather than basal conditions (Nowak et al, 1995) suggests that testosterone may interfere with ACTH signaling at the adrenal. While testosterone-related decreases in ACTH bioactivity have been observed in vitro (Coyne and Kitay, 1969), the Figure 2 Ratio of CRH-stimulated cortisol and ACTH values (mean7SE) during induced hypogonadal (leuprolide plus placebo) and testosterone replaced (leuprolide plus testosterone) conditions.…”

Section: Discussionmentioning

confidence: 73%

“…The effect of testosterone on cortisol, however, appears to be confined to stimulated levels, as no difference in either basal cortisol or UFC was observed across the induced hormonal conditions. Using dispersed inner adrenocortical cells, Nowak et al (1995) showed that testosterone inhibited ACTH-stimulated but not basal corticosterone output in vitro. As testosterone reduced both pregnenolone and (particularly) postpregnenolone steroid levels in this model, both the conversion of cholesterol to pregnenolone and the activities of several steroidogenic enzymes (3bHSD, P450C21, and P450C11) appear to be inhibited (Stalvey, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The consequent suggestion that testosterone inhibition of stimulated cortisol is mediated by the testosterone metabolite estradiol is contradicted by several factors. First, while data are inconsistent, many in vitro and in vivo studies are convergent in showing that estradiol enhances rather than inhibits corticosteroid secretion at the level of both the adrenal (Nowak et al, 1995;Fukui et al, 1961;Kitay, 1961a) and the pituitary (Kitay, 1963;McCormick et al, 2002;Giussani et al, 2000). Second, consistent with this possibility (and more immediately relevant) is the demonstration by Kirschbaum et al (1996) of increased cognitive stress-stimulated cortisol (and ACTH) secretion during short-term estradiol administration to young men; increased mean plasma cortisol concentrations during estradiol administration were also observed in castrated male macaques (Norman et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Testosterone Suppression of CRH-Stimulated Cortisol in Men

Rubinow

Roca

Schmidt

et al. 2005

Neuropsychopharmacol

134

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Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRHstimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (po0.05, 0.005, and 0.01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (po0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (po0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (po0.1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Testosterone Suppression of CRH-Stimulated Cortisol in Men

Rubinow

Roca

Schmidt

et al. 2005

Neuropsychopharmacol

134

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“…However, differences in cortisol secretion in gonadectomised sheep have been found (Broadbear et al, 2005), which were not reverted by sex steroid replacement, although the ewes were replaced with luteal phase levels of progesterone and oestrogens, which means oestrogens were at nadir. In rats, gonadectomy reduces or eliminates sexual differences in HPA function (Nowak et al, 1995). This discrepancy in the effect of gonadectomy on cortisol secretion in sheep suggests that other factors are involved in the cortisol response to ACTH administration.…”

Section: Discussionmentioning

confidence: 99%

“…The most straightforward mechanism would be for the sex steroids to affect adrenocortical sensitivity to ACTH (Atkinson and Waddell, 1997). A stimulating action of oestrogens and an inhibiting action of testosterone on the adrenal have been previously proposed in rats (Kitay, 1963;Nowak et al, 1995). Therefore, one of our target genes in experiment 2 was of the ACTH receptor (MC2R).…”

Section: Adrenal Weightmentioning

confidence: 99%

Sex steroid modulation of cortisol secretion in sheep

Lier

Carriquiry

Meikle

2014

Animal

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There is strong evidence that the gonads modulate the hypothalamic-pituitary-adrenal axis. To investigate these sex differences at the adrenal glands of sheep we compared the cortisol response to ACTH (experiment 1) and measured the relative expression of oestrogen receptor alpha (ERS1), androgen receptor (AR), melanocortin 2 receptor (MC2R) and steroid acute regulatory protein (STAR) mRNA in adrenal glands (experiment 2) of gonadectomised rams and ewes either with or without sex steroid replacement. In experiment 1 six castrated adult rams and four ovariectomised adult ewes were used in two ACTH trials. On each trial blood samples were taken every 15 min for 4 h through an indwelling jugular catheter and each animal received 0.5 mg of an ACTH analogue i.v., immediately after the sample at 1 h from the beginning of the trial. Four days after the first trial the males received 100 mg of Testosterone Cyclopentilpropionate (TC) i.m. and the females received 2.5 mg of Oestradiol Benzoate (EB) i.m. At 72 h after TC or EB administration the second trial was performed. In experiment 2 the adrenal glands were obtained from gonadectomised adult rams (n = 8) and adult ewes (n = 8). Four rams received 100 mg of TC i.m. and four females received 0.5 mg of EB i.m. Blood samples were taken at 0, 12, 24, 48 and 72 h relative to steroid replacement and the animals were thereafter slaughtered. Cortisol, testosterone and 17β-oestradiol were determined by radioimmunoanalysis. The transcripts of ERS1, AR, MC2R and STAR were determined by real-time reverse transcription PCR in adrenal tissue. Cortisol secretion was higher in female sheep than in male sheep, and higher in EB-treated than non-treated ewes. No difference in cortisol secretion was observed between TC-treated and non-treated rams. Gonadectomised rams treated with TC presented greater AR mRNA and MC2R mRNA expression than males without the steroid replacement. Gonadectomised ewes treated with EB tended to present lower AR mRNA than the ones without steroid replacement. Gonadectomised rams with TC also had greater AR mRNA, ERS1 mRNA and MC2R mRNA expression than ewes treated with EB. The relative amount of STAR transcript was not different among the different groups. The results confirm sex differences in ACTH-induced cortisol secretion in sheep, as well as in the expression of the receptor proteins for both 17β-oestradiol and testosterone in the sheep adrenal gland. However, the underlying mechanisms for sex steroid modulation remain unresolved.Keywords: sex steroids, gonadectomy, adrenal, receptors, sheep ImplicationsDifferent stressors result in different responses from the hypothalamus-pituitary-adrenal (HPA) axis and stress can reduce reproductive performance in mammals. Considering the different roles of males and females in reproduction, it is reasonable to think that each sex has its own strategy for dealing with the effects of stress. There is abundant evidence that the gonads affect the way the HPA axis responds to stress. Understanding the regulatory pathways of...

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Effects of estradiol on aldosterone secretion in ovariectomized rats

Kau

Lo²,

Tsai³

et al. 1999

J. Cell. Biochem.

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The effects and action mechanisms of estradiol on aldosterone secretion in female rats were studied. Replacement of estradiol benzoate (EB) increased the levels of plasma estradiol and aldosterone in ovariectomized (Ovx) rats. The aldosterone release from zona glomerulosa (ZG) cells was higher in EB-treated rats than in oil-treated animals. EB treatment potentiated the responses of aldosterone release to adrenocorticotropic hormone (ACTH), forskolin (FSK), and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP). Administration of EB in vivo did not alter cAMP production in response to ACTH or FSK. Although angiotensin II (Ang II) increased aldosterone secretion by rat ZG cells, the stimulatory effect of Ang II on the release of aldosterone was not altered by EB treatment. The conversions of [3H]-deoxycorticosterone to [3H]-corticosterone and [3H]-corticosterone to [3H]-aldosterone in EB-treated groups were greater than those in the oil-treated group. These results suggest that estradiol increases aldosterone secretion in part through the mechanisms involving the activation of the post-cAMP pathway, 11beta-hydroxylase and aldosterone synthase activity.

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Effects of sex hormones on the steroidogenic activity of dispersed adrenocortical cells of the rat adrenal cortex

Cited by 56 publications

References 17 publications

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Sex steroid modulation of cortisol secretion in sheep

Effects of estradiol on aldosterone secretion in ovariectomized rats

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