The extragonadal biology of gonadotropin hormones: should we rename these?

Over recent years, gonadotropins and their receptors have been shown to exert non-traditional actions that bypass the classical hypothalamic-pituitary-gonadal axis. Findings of the expression of receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in skeletal, fat, and immune cells and in neurons suggest that their functions are much broader than their classical roles. FSH, once believed solely to regulate procreation-gonadal development and maturation at puberty and gamete production during the fertile phase, has been found to regulate body composition, bone metabolism, and cognition, providing the underpinnings of complex integrative physiology, and, in turn, opening potential new therapeutic opportunities. Pre-clinical evidence from genetic and pharmacologic interventions in rodent models and human data from population-based observations, genetic studies, and a small number of interventional studies together support the independent skeletal, adipogenic, and cognitive actions of gonadotropins. Here, we review our current understanding of direct actions of FSH and LH on bone, adipose tissue, and brain and focus specifically on the detrimental health burden during and after the menopause: osteoporosis, obesity, and dementia.