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Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-2376-5952
Article

Activation of Follicle-Stimulating Hormone Receptor in Adrenal Zona Fasciculata Cells Promotes Cortisol Secretion: Implications for the Development of Menopause-Associated Diseases

Jing-Gen Wu‡
1   Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
,
Peng Zhao‡
1   Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
,
Jing Yang‡
3   Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
,
Ming-Juan Wang
1   Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
,
Jian-Hua Chen
2   Department of Pathology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
,
Xiao-Yong Li
1   Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
,
Xue Ying
1   Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
,
Yong-Chao Lu
1   Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
› Author Affiliations Funding Information This study was supported by the National Natural Science Foundation of China (81671418), the Open Project of the Key Laboratory for Birth Defects Prevention of the National Health Commission (ZD202202), and the National Key Research and Development Program of China (2018YFC1003202).
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Abstract

Objective Changes in postmenopausal hormone levels are associated with a variety of disorders. This study elucidated the mechanism by which follicle-stimulating hormone (FSH) increases cortisol production involved in development of menopause-related diseases.

Methods The expression of FSH receptors (FSHRs) in murine adrenal zona fasciculata (AZF) cells and ATC7 cells was verified by immunofluorescence, western blotting and RT–PCR. The function of FSHR in promoting cortisol production was analyzed by cell culture and molecular biological methods. FSHR signaling pathways in ATC7 cells were analyzed by ELISA, qRT–PCR, and western blotting. Further, a mouse model was established by ovariectomy. Ovariectomized mice were treated with GnRHa. Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH. Then serum FSH, luteinizing hormone (LH), estradiol, and cortisol, and bone mineral density (BMD), blood pressure (BP) and heart rate (HR) were determined.

Results FSHRs were expressed in murine AZF cells and ATC7 cells. FSH accelerated cortisol production through activated protein kinase A (PKA), cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), protein kinase B (PKB/AKT) and 5ʼ AMP-activated protein kinase (MAPK) signaling pathways by Gsα-coupled FSHRs in ATC7 cells. Serum FSH levels (P<0.001) were elevated in ovariectomized mice with concurrent increases in cortisol (P<0.01), areal BMD (aBMD) (P<0.05), volumetric BMD (vBMD) (P<0.05), systolic BP (SBP) (P<0.05), diastolic BP (DBP) (P<0.05), and HR (P<0.05). However, the administration of GnRHa suppressed the increase in FSH levels and the elevation of cortisol, aBMD, vBMD, SBP, DBP, and HR induced by ovariectomy, even in the presence of normal serum estradiol levels.

Conclusion The study findings indicate that elevated FSH levels stimulate cortisol secretion, through a mechanism related to FSHRs expression in AZF cells.

Keywords

follicle-stimulating hormone receptor - adrenal zona fasciculata cells - cortisol - menopause - ovariectomy

Supplementary Material



Publication History

Received: 15 January 2024
Received: 12 July 2024

Accepted: 18 July 2024

Article published online:
16 September 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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