Injection of luteinizing hormone or human chorionic gonadotropin increases calcium excretion and serum PTH in males

• Published in: Cell calcium (Edinburgh) Vol. 122; p. 102908
• Main Authors: Juel Mortensen, Li, Kooij, Ireen, Lorenzen, Mette, Rye Jørgensen, Niklas, Røder, Andreas, Jørgensen, Anne, Andersson, Anna-Maria, Juul, Anders, Blomberg Jensen, Martin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2024
• Subjects: Calcium; Calcium homeostasis; Endocrine cross-talk; Excretion; Human chorionic gonadotropin; LHCGR expression; Luteinizing hormone; Males; Translational research; Excretion; Translational research; Calcium; Human chorionic gonadotropin; Luteinizing hormone; Endocrine cross-talk; LHCGR expression; Males; Calcium homeostasis
• ISSN: 0143-4160; 1532-1991; 1532-1991
• DOI: 10.1016/j.ceca.2024.102908

•In mice, luteinizing hormone (LH) treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone.•In healthy men, human-chorionic-gonadotropin (hCG) injections led to a significant increase in urinary calcium excretion, and increase in serum PTH levels, and calcitriol (1,25 (OH)2D3).•The common receptor for LH and hCG, LHCGR, is expressed in human kidney tissue.•LHCGR may be influencing calcium homeostasis directly or indirectly. Animal and human studies have suggested that sex steroids have calciotropic actions, and it has been proposed that follicle-stimulating hormone (FSH) may exert direct effects on bone. Here, we demonstrate the expression of the receptor for Luteinizing hormone (LH) and human choriogonadotropin (hCG), LHCGR, in human kidney tissue, suggesting a potential influence on calcium homeostasis. To investigate the role of LHCGR agonist on calcium homeostasis in vivo, we conducted studies in male mice and human subjects. Male mice were treated with luteinizing hormone (LH), and human extrapolation was achieved by injecting 5000 IU hCG once to healthy men or men with hypergonadotropic or hypogonadotropic hypogonadism. In mice, LH treatment significantly increased urinary calcium excretion and induced a secondary increase in serum parathyroid hormone (PTH). Similarly, hCG treatment in healthy men led to a significant increase in urinary calcium excretion, serum PTH levels, and 1,25 (OH)2D3, while calcitonin, and albumin levels were reduced, possibly to avoid development of persistent hypocalcemia. Still, the rapid initial decline in ionized calcium coincided with a significant prolongation of the cardiac QTc-interval that normalized over time. The observed effects may be attributed to LH/hCG-receptor (LHCGR) activation, considering the presence of LHCGR expression in human kidney tissue, and the increase in sex steroids occurred several hours after the changes in calcium homeostasis. Our translational study shed light on the intricate relationship between gonadotropins, sex hormones and calcium, suggesting that LHCGR may be influencing calcium homeostasis directly or indirectly. [Display omitted]