Regulatory mechanism of ghrelin on testosterone secretion in type 1 diabetic rats.

Abstract

Abstract: Ghrelin, which is a hormone composed of 28 amino acids that is mainly produced in the stomach, is also secreted by Leydig cells in the testes of rats and humans. The hypothalamus regulates testosterone secretion by releasing gonadotropin-releasing hormone (GnRH), which stimulates the pituitary gland to release luteinizing hormone (LH). LH then prompts the testes to produce testosterone via the activity of steroidogenic acute regulatory protein (StAR). Consequently, ghrelin may play a regulatory role in gonadal function. Male Sprague-Dawley rats were randomly assigned to four groups: the control, ghrelin-treated, diabetic, and diabetic plus ghrelin treatment groups. After the rats were sacrificed, plasma samples were collected. Leydig cells were isolated and cultured with human chorionic gonadotropin (hCG, which is similar to LH and is used to stimulate Leydig cells to synthesize testosterone), 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP, which is an activator of cyclic adenosine monophosphate-dependent protein kinase), or forskolin (an activator of adenylyl cyclase in a wide variety of cell types). Compared with normal treatment, ghrelin treatment in diabetic rats markedly increased plasma testosterone levels by 3.75-fold (P < 0.05), Leydig cell testosterone secretion by 2.8-fold (P < 0.05), GnRH-mediated LH release from the anterior pituitary by 2.95-fold (P < 0.05), and StAR expression by 1.96-fold (P < 0.05) in testicular Leydig cells. These findings indicated that ghrelin enhanced testosterone production in diabetic rats, which was partially achieved by the hypothalamic-pituitary-gonadal axis and StAR. This study emphasized the potential use of ghrelin as a treatment for improving testosterone levels and gonadal function in individuals with diabetes.

Lay summary: This study explored how a hormone known as ghrelin (which is mainly produced in the stomach) may help in regulating testosterone levels. Researchers examined male rats in four groups, including diabetic rats treated with ghrelin, and discovered that ghrelin increased testosterone production in diabetic rats by improving the communication between the brain, pituitary gland, and testes. This hormone also helped specific cells in the testes to function more effectively. The diabetic rats treated with ghrelin exhibited notable increases in testosterone levels and improved hormone function. These findings suggest that ghrelin could potentially help to address hormonal imbalances related to diabetes and improve reproductive health. This research highlights the potential benefits of ghrelin in addressing hormonal imbalances.