Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver. New evidence also indicates that pituitary hormone receptors are expressed in brain regions, nuclei and subnuclei. These studies have prompted us to attribute the pathophysiology of certain human diseases, including osteoporosis, obesity and neurodegeneration, at least in part, to changes in pituitary hormone levels. This new information has identified actionable therapeutic targets for drug discovery.
Contrary to textbook physiology, pituitary hormones have ubiquitous functions and are the basis of important regulatory circuits that continue to evolve.
Endocrine diseases, such as osteoporosis, that were traditionally attributed to a single effector hormone are far more complicated than originally thought.
Pituitary hormones, such as follicle-stimulating hormone, act directly on both peripheral and central targets to contribute to the development of several diseases, such as osteoporosis, obesity and Alzheimer disease.
The pituitary–multiorgan circuitry could be exploited therapeutically to prevent and treat diseases driven by pituitary hormones.
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Work at Icahn School of Medicine at Mount Sinai carried out at the Center for Translational Medicine and Pharmacology was supported by R01 AG071870 to M.Z., T.Y. and S.-M.K.; R01 AG074092 and U01 AG073148 to T.Y. and M.Z.; and U19 AG060917 and R01 DK113627 to M.Z. M.Z. also thanks the Harrington Discovery Institute for the Innovator-Scholar Award towards the development of anti-FSH antibody. The authors are grateful to V. Ryu (Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA) for his insights on the central actions of pituitary hormones.
M.Z. is an inventor on issued patents on inhibiting FSH for the prevention and treatment of osteoporosis and obesity (US Patents 8,435,948 and 11,034,761). M.Z. is also an inventor on a patent application on the composition and use of humanized monoclonal anti-FSH antibodies and is a co-inventor of a pending patent on the use of FSH as a target for preventing Alzheimer disease. M.Z. and T.Y. are co-inventors on a pending patent application relating to the effect of luteinizing hormone on body composition and another patent relating to the ultra-high formulation of an FSH-blocking antibody. These patents are owned by Icahn School of Medicine at Mount Sinai (ISMMS), and the inventors and co-inventors would be recipients of royalties, per institutional policy. M.Z. also consults for Rani Pharmaceuticals, and several financial platforms, including Gerson Lehman Group and Guidepoint, on drugs for osteoporosis and genetic bone diseases. S.-M.K. declares no competing interests.
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Zaidi, M., Yuen, T. & Kim, SM. Pituitary crosstalk with bone, adipose tissue and brain. Nat Rev Endocrinol 19, 708–721 (2023). https://doi.org/10.1038/s41574-023-00894-5