Stimulatory Effect of Intermittent Hypoxia on the Production of Corticosterone by Zona Fasciculata-Reticularis Cells in Rats

Guey-Shyang Hwang,Shyi-Wu Wang,Paulus S Wang,Jou-Chun Chou,Sindy Hu,Shu-Fen Kan,Fu-Kong Lieu,Ling-Ling Chang,Wei-Ho Lai,Chih-Chieh Chen

doi:10.1038/s41598-017-07054-6

Abstract

Hypoxia or intermittent hypoxia (IH) have known to alter both synthesis and secretion of hormones. However, the effect of IH on the production of adrenal cortical steroid hormones is still unclear. The aim of present study was to explore the mechanism involved in the effect of IH on the production of corticosterone by rat ZFR cells. Male rats were exposed at 12% O2 and 88% N2 (8 hours per day) for 1, 2, or 4 days. The ZFR cells were incubated at 37 °C for 1 hour with or without ACTH, 8-Br-cAMP, calcium ion channel blockers, or steroidogenic precursors. The concentration of plasma corticosterone was increased time-dependently by administration of IH hypoxia. The basal levels of corticosterone production in cells were higher in the IH groups than in normoxic group. IH resulted in a time-dependent increase of corticosterone production in response to ACTH, 8-Br-cAMP, progesterone and deoxycorticosterone. The production of pregnenolone in response to 25-OH-C and that of progesterone in response to pregnenolone in ZFR cells were enhanced by 4-day IH. These results suggest that IH in rats increases the secretion of corticosterone via a mechanism at least in part associated with the activation of cAMP pathway and steroidogenic enzymes.

Highlights

Hypoxia induces disorders of the brain-endocrine-immune network through activation of corticotropin-releasing hormone (CRH) and corticotropin-releasing hormone receptor 1 (CRHR1) in the brain and periphery including activation of the hypothalamus–pituitary–adrenal (HPA) axis in a time- and dose-dependent manner[7]
The objectives of the present work are to explore the effects of intermittent hypoxia (8 hours per day for 0, 1 or 4 days) on the release of corticosterone in response to some stimulants including ACTH, 8-Br-cAMP, Ca2+ channel blockers, and steroidogenic precusors to detect the involvement of cAMP pathway, calcium channels and activities of steroidogenic enzymes during biosynthesis and secretion of corticosterone
The present results suggested that intermittent hypoxia increased the production of corticosterone in rats, via an increase of the activities of [1] c-AMP [2] L- and T-type calcium channels as well as enzyme activities of P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 21β-hydroxylase and 11β-hydroxylase

Summary

Introduction

Hypoxia induces disorders of the brain-endocrine-immune network through activation of corticotropin-releasing hormone (CRH) and corticotropin-releasing hormone receptor 1 (CRHR1) in the brain and periphery including activation of the hypothalamus–pituitary–adrenal (HPA) axis in a time- and dose-dependent manner[7]. This results in the release of CRH which stimulates the release of ACTH from the pituitary gland and the release of glucocorticoid hormones from the adrenal cortex (corticosterone in most rodents; cortisol in humans). Our hypothesis is that intermittent hypoxia acts through the pathways of the actions of ACTH and cAMP, calcium channel, and cholesterol side-chain cleavage enzyme (P450scc) to affect the secretion of corticosterone by zona fasciculata-reticularis cells. The objectives of the present work are to explore the effects of intermittent hypoxia (8 hours per day for 0, 1 or 4 days) on the release of corticosterone in response to some stimulants including ACTH, 8-Br-cAMP, Ca2+ channel blockers, and steroidogenic precusors to detect the involvement of cAMP pathway, calcium channels and activities of steroidogenic enzymes during biosynthesis and secretion of corticosterone

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