Journal of Clinical Endocrinology & Metabolism, Vol 71, 900-906, Copyright © 1990 by Endocrine Society

ARTICLES

Marked attenuation of ultradian and circadian rhythms of dehydroepiandrosterone in postmenopausal women: evidence for a reduced 17,20-desmolase enzymatic activity

CH Liu, GA Laughlin, UG Fischer and SS Yen
Department of Reproductive Medicine, School of Medicine, University of California-San Diego, La Jolla 92093.

Circulating levels of adrenal delta 5-androgens [dehydroepiandrosterone (DHEA), and its sulfate (DS)] selectively decrease with age in both sexes, while cortisol secretion remains unchanged. The mechanism(s) to account for this dissociation is unclear. We tested the hypothesis that a reduced enzymatic activity for delta 5-androgen biosynthesis may be responsible for this phenomenon by examining the ultradian and circadian rhythmicity (15-min sampling frequency for 24 h) of DHEA and cortisol and the responsiveness of DHEA, DS, and cortisol to human CRF stimulation and by the analysis of relative enzymatic activities in the biosynthesis of adrenal steroids in older postmenopausal women (PMW) and younger cycling women (NCW). Our data show that the timing of the circadian rhythm of DHEA secretion was not altered, but the acrophase amplitude was decreased (P less than 0.01) in aged PMW compared to NCW. While the pulse frequency of DHEA remained unchanged, the pulse amplitude was markedly attenuated in PMW compared with NCW (3.5 +/- 0.6 vs. 8.1 +/- 1.1 nmol/L; P less than 0.01). Correspondingly, the 24-h mean of DHEA was markedly reduced (P less than 0.001) in PMW (5.5 +/- 0.8 nmol/L) from that in NCW (12.1 +/- 1.4 nmol/L). For cortisol, all parameters were similar between the two groups. Thus, compared to NCW, the decline of circulating DHEA level in PMW was expressed by attenuations of pulse amplitude and circadian amplitude, without changes in the timing of the circadian rhythm or pulse frequency. Further, DHEA and DS, but not cortisol, responses to 8-h hCRF infusion were significantly (P less than 0.01) diminished in PMW. These findings together with decreased product/precursor ratios for DHEA/17- hydroxypregnenolone (P less than 0.01) and androstenedione/17- hydroxyprogesterone (P less than 0.05) suggest a reduction of 17,20- desmolase enzymatic activity in PMW compared to that in NCW. Steroid ratios for 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase were unaltered. We conclude from these preliminary data that the disparity of DHEA and cortisol secretion in aged PMW is probably related to an intraadrenal event, resulting from a decrease in 17,20- desmolase expression, which governs the biosynthesis of delta 5-adrenal androgen.

This article has been cited by other articles:

				R. Giordano, M. Bo, M. Pellegrino, M. Vezzari, M. Baldi, A. Picu, M. Balbo, L. Bonelli, G. Migliaretti, E. Ghigo, et al. Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5656 - 5662. [Abstract] [Full Text] [PDF]

				S. Dharia, A. Slane, M. Jian, M. Conner, A. J. Conley, R. M. Brissie, and C. R. Parker Jr. Effects of Aging on Cytochrome B5 Expression in the Human Adrenal Gland J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4357 - 4361. [Abstract] [Full Text] [PDF]

				F. Labrie, V. Luu-The, C. Labrie, A. Belanger, J. Simard, S.-X. Lin, and G. Pelletier Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone Endocr. Rev., April 1, 2003; 24(2): 152 - 182. [Abstract] [Full Text] [PDF]

				B. L. Lasley, N. Santoro, J. F. Randolf, E. B. Gold, S. Crawford, G. Weiss, D. S. McConnell, and M. F. Sowers The Relationship of Circulating Dehydroepiandrosterone, Testosterone, and Estradiol to Stages of the Menopausal Transition and Ethnicity J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3760 - 3767. [Abstract] [Full Text] [PDF]

				B. Breuer, C. Martucci, S. Wallenstein, A. Likourezos, L. S. Libow, A. Peterson, and B. Zumoff Relationship of Endogenous Levels of Sex Hormones to Cognition and Depression in Frail, Elderly Women Am J Geriatr Psychiatry, June 1, 2002; 10(3): 311 - 320. [Abstract] [Full Text] [PDF]

				S. S. C. Yen Dehydroepiandrosterone sulfate and longevity: New clues for an old friend PNAS, July 17, 2001; 98(15): 8167 - 8169. [Full Text] [PDF]

				G. A. Laughlin and E. Barrett-Connor Sexual Dimorphism in the Influence of Advanced Aging on Adrenal Hormone Levels: The Rancho Bernardo Study J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3561 - 3568. [Abstract] [Full Text]

				A. J. Alberg, G. B. Gordon, S. C. Hoffman, G. W. Comstock, and K. J. Helzlsouer Serum Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate and the Subsequent Risk of Developing Colon Cancer Cancer Epidemiol. Biomarkers Prev., May 1, 2000; 9(5): 517 - 521. [Abstract] [Full Text]

				C. R. Parker Jr., S. M. Slayden, R. Azziz, S. L. Crabbe, G. A. Hines, L. R. Boots, and S. Bae Effects of Aging on Adrenal Function in the Human: Responsiveness and Sensitivity of Adrenal Androgens and Cortisol to Adrenocorticotropin in Premenopausal and Postmenopausal Women J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 48 - 54. [Abstract] [Full Text]

				S. M. Slayden, L. Crabbe, S. Bae, H. D. Potter, R. Azziz, and C. R. Parker Jr. The Effect of 17{beta}-Estradiol on Adrenocortical Sensitivity, Responsiveness, and Steroidogenesis in Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 519 - 524. [Abstract] [Full Text]