Patterns of Acth and Cortisol Pulsatility Over Twenty‐four Hours in Normal Males and Females

Horrocks, P. M.; Jones, A. F.; Ratcliffe, W. A.; Holder, G.; White, Anne; Holder, Roger; Ratcliffe, John G.; London, David

doi:10.1111/j.1365-2265.1990.tb03758.x

Cited by 150 publications

(88 citation statements)

References 8 publications

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“…In fact, as measured by the cortisol : ACTH ratio, adrenal sensitivity tended to decrease on testosterone þ leuprolide relative to placebo þ leuprolide, with the reduction primarily reflecting the two-fold decrease in the ratio at time points 120-150, again suggesting diminished cortisol response to ACTH. Reductions in adrenal sensitivity have been postulated to explain similar cortisol values in young men and women despite significantly elevated ACTH levels in the young men (Roelfsema et al, 1993;Horrocks et al, 1990;Kudielka et al, 2004). The present data would suggest even greater modulation of adrenal sensitivity by testosterone, as not only is ACTH significantly higher but cortisol is also significantly lower compared with the hypogonadal state.…”

Section: Discussionsupporting

confidence: 51%

“…Supportive data include observations of sex differences in hypothalamic-pituitaryadrenal (HPA) axis activity/responsivity (Kitay, 1961b;Brett et al, 1983;Horrocks et al, 1990;Kirschbaum et al, 1992;McCormick et al, 2002;Roelfsema et al, 1993;Greenspan et al, 1993) and demonstration of acute regulatory effects of gonadal steroids on the HPA axis in animal castration and replacement studies (Kitay, 1963;Burgess and Handa, 1992;Critchlow et al, 1963;Bingaman et al, 1994). As the first observations of sex differences showed increased HPA axis activity in female rodents, most attention has focused on the effects of estradiol, with little attention paid to the possible modulatory role of testosterone.…”

Section: Introductionmentioning

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: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Rubinow

Roca

Schmidt

et al. 2005

Neuropsychopharmacol

134

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“…32 The mean corticotropin concentration and the 24-hour corticotropin AUC was significantly larger in the male group without any difference in the 24-hour cortisol AUC or in the mean cortisol concentration, suggesting that the female adrenal cortex may be more sensitive to corticotropin, Thus any equivalent reduction in corticotropin secretion should yield a larger cortisol suppressive effect in the female group. Our study also did not find a difference in the mean cortisol concentration (calculated as R m /k c ) or 24-hour cortisol AUC between genders.…”

Section: Pharmacodynamicsmentioning

confidence: 89%

“…Horrocks et al 32 studied plasma corticotropin and cortisol concentrations in five men and five premenopausal women (during the follicular phase of their menstrual cycle) over a 24-hour period. 32 The mean corticotropin concentration and the 24-hour corticotropin AUC was significantly larger in the male group without any difference in the 24-hour cortisol AUC or in the mean cortisol concentration, suggesting that the female adrenal cortex may be more sensitive to corticotropin, Thus any equivalent reduction in corticotropin secretion should yield a larger cortisol suppressive effect in the female group.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

Lew

Ludwig

Milad

et al. 1993

Clin Pharmacol Ther

155

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The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC 50 ) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC 50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response.Male subjects typically have been used in most drug studies. However, the findings of these studies are applied clinically to both male and female patients, despite their physiologic differences. Of the studies that have enrolled both men and women, most fail to analyze their findings by gender and instead treat all the subjects as one homogeneous group. 1 This bias in clinical research has been of concern within the health professions. [2][3][4] The literature currently lacks guidelines regarding dosing regimens based on gender.Copyright © 1993 by Mosby-Year Book, Inc.Reprint requests: William J. Jusko, PhD, Hochstetter 565, School of Pharmacy, State University or New York at Buffalo, Buffalo, NY 14260. Presented at the Ninety-fourth Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, March 24-26, 1993, Honolulu, Hawaii (Abstract: Clin Pharmacol Ther 1993;53:183). NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2014 October 23. Published in final edited form as:Clin Pharmacol Ther. 1993 October ; 54(4): 402-414. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptGender-related differences in disposition have been observed for numerous drugs. The total and unbound clearance of diazepam, which undergoes oxidative metabolism, was found to be greater in women. 5 Clearance of oxazepam (total and unbound) 6 and acetaminophen, 7 both of which undergo glucuronide conjugation, is significantly greater ...

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“…[34] In nonstressful situations, both CRH and AVP are secreted in the portal system in a circadian and highly concordant pulsatile fashion. [35][36][37][38][39][40] The amplitude of the CRH and AVP pulses increases in the early morning, resulting eventually in increases in the amplitude and apparent frequency of ACTH and in cortisol secretory bursts in the general circulation. The circadian release of CRH, AVP, ACTH, and cortisol in their characteristic pulsatile manner appears to be controlled by one or more pacemakers, whose location in humans is not known.…”

Section: Hypothalamic-pituitary-adrenal Axismentioning

confidence: 99%

Organization and Integration of the Endocrine System: The Arousal and Sleep Perspective

Chrousos

2007

Sleep Medicine Clinics

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Patterns of Acth and Cortisol Pulsatility Over Twenty‐four Hours in Normal Males and Females

Cited by 150 publications

References 8 publications

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Testosterone Suppression of CRH-Stimulated Cortisol in Men

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

Organization and Integration of the Endocrine System: The Arousal and Sleep Perspective

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