Journal of Clinical Endocrinology & Metabolism, Vol 62, 413-418, Copyright © 1986 by Endocrine Society

ARTICLES

Steroid inhibitory effects upon human adrenal 3 beta-hydroxysteroid dehydrogenase activity

GC Byrne, YS Perry and JS Winter

The inhibitory effects of varying concentrations of steroids upon 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta- HSD) kinetics were studied in human adrenal microsomes. Each enzyme assay was conducted in triplicate at five different concentrations of three substrates (dehydroepiandrosterone, pregnenolone, and 17OH- pregnenolone), using microsomes from at least three donors. Each steroid was screened for possible inhibition at concentrations of 10(- 8) and 10(-6) M and then studied in more detail at five different concentrations. The type of inhibition and the inhibition constant (Ki) were determined by analysis of Lineweaver-Burk and Dixon plots, together with replots of the slopes from the Dixon plots. The mean Km (Michaelis-Menten constant) for the three substrates was 0.42 +/- 0.04 (SE) mumol/liter (n = 73). Each steroid tested, including delta 5-3 beta-hydroxysteroids, estrogens, and several delta 4-3-ketosteroids, with the exception of cortisol, caused significant inhibition of 3 beta- HSD activity, and in each case the steroid appeared to behave as a competitive inhibitor. In most cases the Ki value was approximately 10(- 7) M. At micromolar concentrations several steroids, notably estrone and estradiol, caused almost total inhibition of adrenal 3 beta-HSD activity. Comparison of the calculated Ki values with available data concerning changes in intra-adrenal steroid concentrations during childhood suggests that these changes would be sufficient to cause a relative decline in 3 beta-HSD activity during adrenarche. Although postnatal circulating steroid concentrations would appear to be insufficient to influence adrenal steroidogenesis, the high serum levels of placental steroids during fetal life would be expected to cause marked 3 beta-HSD inhibition.

This article has been cited by other articles:

				S. Ben-David, N. Zuckerman-Levin, M. Epelman, Z. Shen-Orr, M. Levin, P. Sujov, and Z. Hochberg Parturition Itself Is the Basis for Fetal Adrenal Involution J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 93 - 97. [Abstract] [Full Text] [PDF]

				M. H. Bassett, T. Suzuki, H. Sasano, C. J. M. de Vries, P. T. Jimenez, B. R. Carr, and W. E. Rainey The Orphan Nuclear Receptor NGFIB Regulates Transcription of 3{beta}-Hydroxysteroid Dehydrogenase: IMPLICATIONS FOR THE CONTROL OF ADRENAL FUNCTIONAL ZONATION J. Biol. Chem., September 3, 2004; 279(36): 37622 - 37630. [Abstract] [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]

				G. A. Brown, M. D. Vukovich, R. L. Sharp, T. A. Reifenrath, K. A. Parsons, and D. S. King Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men J Appl Physiol, December 1, 1999; 87(6): 2274 - 2283. [Abstract] [Full Text] [PDF]

				S. Mesiano, S. L. Katz, J. Y. Lee, and R. B. Jaffe Phytoestrogens Alter Adrenocortical Function: Genistein and Daidzein Suppress Glucocorticoid and Stimulate Androgen Production by Cultured Adrenal Cortical Cells J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2443 - 2448. [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]