FSH-metabolic circuitry and menopause

Abstract

FSH has a primary function in procreation, wherein it induces estrogen production in females and regulates spermatogenesis in males. However, in line with our discoveries over the past decade of non-unitary functions of pituitary hormones, we and others have described hitherto uncharacterized functions of FSH. Through high-affinity receptors, some of which are variants of the ovarian FSH receptor (FSHR), FSH regulates bone mass, adipose tissue function, energy metabolism, and cholesterol production in both sexes. These newly described actions of FSH may indeed be relevant to the pathogenesis of bone loss, dysregulated energy homeostasis, and disordered lipid metabolism that accompany the menopause in females and aging in both genders. We are therefore excited about the possibility of modulating circulating FSH levels toward a therapeutic benefit for a host of age-associated diseases, including osteoporosis, obesity and dyslipidemia, among other future possibilities.

Recent advances in understanding gonadotropin signaling

“…Genetically modified or antibody-treated mouse models elegantly suggested that FSH-induced signals modulate bone mass and adipose tissue 123 , 250 . Around these issues, several studies described a link between FSH, osteoporosis, and increased fat mass that occurs after menopause 251 – 258 . Similar conclusions were achieved by in vitro studies using human cells 259 , 260 , although the existence of direct causality between gonadotropin receptor and the physiological effect was questioned 261 .…”

Vasomotor menopausal disorders as a possible result of dysfunction of the microbiota-intestine-brain axis

“…The climacteric period is a physiological period in a woman’s life, corresponding to the transition from the reproductive phase to post menopause. According to the generally accepted concept, significant transformations occur in the functioning of the hypothalamic-pituitary-gonadal axis during this stage, against the background of general age-related changes in the body [ 1 , 2 ]. Thus, according to the data of numerous research, involutive processes in the female reproductive system are accompanied by a progressive increase in the level of follicle-stimulating hormone (FSH), a decrease in the concentrations of estradiol (E2), anti-mullerian hormone, and inhibin B, which is caused by gradual depletion of the ovarian follicular reserve, a decrease in the frequency of the ovulatory cycles, acceleration of follicular atrophy and atresia, as well as a decrease in the expression of receptors to gonadotropins (FSH, luteinizing hormone (LH)) [ 3 , 4 ].…”

PTPN5 promotes follicle‐stimulating hormone secretion through regulating intracellular calcium homeostasis

“…3 Many studies established that FSH levels become elevated combined with a decrease of estrogen in menopause. 4 Estrogen regulates the gene expression through genomic signaling pathways and non-genomic signaling pathways. Estrogen can enter the cell membrane and interact with estrogen receptor (ER), which can mediate non-genomic signaling pathways on the cell membrane and genomic signaling pathways in the cytoplasm.…”

“…Follicle‐stimulating hormone (FSH), a glycoprotein polypeptide hormone, is produced by the anterior pituitary gland, and is ubiquitously considered to function in the regulation of sex hormone synthesis in the gonads 3 . Many studies established that FSH levels become elevated combined with a decrease of estrogen in menopause 4 . Estrogen regulates the gene expression through genomic signaling pathways and non‐genomic signaling pathways.…”