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Stress hormone and male reproductive function

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Abstract

The Leydig cell is the primary source of testosterone in males. Levels of testosterone in circulation are determined by the steroidogenic capacities of individual Leydig cells and the total numbers of Leydig cells per testis. Stress-induced increases in serum glucocorticoid concentrations inhibit testosterone-biosynthetic enzyme activity, leading to decreased rates of testosterone secretion. It is unclear, however, whether the excessive glucocorticoid stimulation also affects total Leydig cell numbers through induction of apoptosis and thereby contributes to the stress-induced suppression of androgen levels. Exposure of Leydig cells to high concentrations of corticosterone (CORT, the endogenously secreted glucocorticoid in rodents) increases their frequency of apoptosis. Studies of immobilization stress indicate that stress-induced increases in CORT are directly responsible for Leydig cell apoptosis. Access to glucocorticoid receptors in Leydig cells is modulated by oxidative inactivation of glucocorticoid by 11β-hydroxysteroid dehydrogenase (11βHSD). Under basal levels of glucocorticoid, sufficient levels of glucocorticoid metabolism occur and there is likely to be minimal binding of the glucocorticoid receptor. We have established that Leydig cells express type 1 11βHSD, an oxidoreductase, and type 2, a unidirectional oxidase. Generation of redox potential through synthesis of the enzyme cofactor NADPH, a byproduct of glucocorticoid metabolism by 11βHSD-1, may potentiate testosterone biosynthesis, as NADPH is the cofactor used by steroidogenic enzymes such as type 3 17β-hydroxysteroid dehydrogenase. In this scenario, inhibition of steroidogenesis will only occur under stressful conditions when high input amounts of CORT exceed the capacity of oxidative inaction by 11βHSD. Changes in autonomic catecholaminergic activity may contribute to suppressed Leydig cell function during stress, and may explain the rapid onset of inhibition. However, recent analysis of glucocorticoid action in Leydig cells indicates the presence of a fast, non-genomic pathway that will merit further investigation.

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Author notes

  1. Qiang Dong

    Present address: Department of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China

Authors and Affiliations

  1. Center for Biomedical Research, Population Council, New York, NY, 10021, USA

    Matthew P. Hardy, Qiang Dong, Renshan Ge & Chantal Sottas

  2. Department of Biochemistry and Molecular Biology, Shanghai Second Medical University, Shanghai, 200025, People's Republic of China

    Hui-Bao Gao, Qian Wang, Wei Ran Chai & Xing Feng

  3. 1230 York Avenue, New York, NY, 10021, USA

    Matthew P. Hardy

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  1. Matthew P. Hardy
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Correspondence to Matthew P. Hardy.

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Hardy, M.P., Gao, HB., Dong, Q. et al. Stress hormone and male reproductive function. Cell Tissue Res 322, 147–153 (2005). https://doi.org/10.1007/s00441-005-0006-2

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  • DOI: https://doi.org/10.1007/s00441-005-0006-2

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