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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/E1039    most recent 00010.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hwang, G.-S. Articles by Wang, S.-W. PubMed PubMed Citation Articles by Hwang, G.-S. Articles by Wang, S.-W.

Effects of hypoxia on testosterone release in rat Leydig cells

¹Department of Nursing, Chang Gung Institute of Technology, Kweisan; ²Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Gung Memorial Hospital, Taoyuan; ³Cancer Translation Research Center, Taiwan Tung Yang Biopharmacy Company, Taipei; and ⁴Department of Physiology, Chang Gung University, Kweisan, Taoyuan, Taiwan

Submitted 4 February 2009 ; accepted in final form 31 July 2009

The aim of this study was to explore the effect and action mechanisms of intermittent hypoxia on the production of testosterone both in vivo and in vitro. Male rats were housed in a hypoxic chamber (12% O₂ + 88% N₂, 1.5 l/ml) 8 h/day for 4 days. Normoxic rats were used as control. In an in vivo experiment, hypoxic and normoxic rats were euthanized and the blood samples collected. In the in vitro experiment, the enzymatically dispersed rat Leydig cells were prepared and challenged with forskolin (an adenylyl cyclase activator, 10^–4 M), 8-Br-cAMP (a membrane-permeable analog of cAMP, 10^–4 M), hCG (0.05 IU), the precursors of the biosynthesis testosterone, including 25-OH-C (10^–5 M), pregnenolone (10^–7 M), progesterone (10^–7 M), 17-OH-progesterone (10^–7 M), and androstendione (10^–7-10^–5 M), nifedipine (L-type Ca²⁺ channel blocker, 10^–6-10^–4 M), nimodipine (L-type Ca²⁺ channel blocker, 10^–5 M), tetrandrine (L-type Ca²⁺ channel blocker, 10^–5 M), and NAADP (calcium-signaling messenger causing release of calcium from intracellular stores, 10^–6-10^–4 M). The concentrations of testosterone in plasma and medium were measured by radioimmunoassay. The level of plasma testosterone in hypoxic rats was higher than that in normoxic rats. Enhanced testosterone production was observed in rat Leydig cells treated with hCG, 8-Br-cAMP, or forskolin in both normoxic and hypoxic conditions. Intermittent hypoxia resulted in a further increase of testosterone production in response to the testosterone precursors. The activity of 17β-hydroxysteroid dehydrogenase was stimulated by the treatment of intermittent hypoxia in vitro. The intermittent hypoxia-induced higher production of testosterone was accompanied with the influx of calcium via L-type calcium channel and the increase of intracellular calcium via the mechanism of calcium mobilization. These results suggested that the intermittent hypoxia stimulated the secretion of testosterone at least in part via stimulatory actions on the activities of adenylyl cyclase, cAMP, L-type calcium channel, and steroidogenic enzymes.