Small molecule agonists and antagonists for the LH and FSH receptors

Abstract

Luteinising hormone (LH) and follicle-stimulating hormone (FSH) play a critical role in human reproduction. LH and FSH are secreted from the pituitary and act on their respective G-protein-coupled receptors (GPCRs), LHR and FSHR, in the gonads to either promote follicular growth and differentiation in women or to stimulate the proper progression of spermatogenesis in men. LH and FSH are currently used in the clinic for the treatment of infertility. Small molecule agonists of LHR and FSHR have the potential to become oral therapeutics for infertility treatment, whereas small molecule antagonists of LHR and FSHR may find utility in oral contraception. Advances in molecular biology, high-throughput screening (HTS) and combinatorial chemistry have made significant contributions to the recent discovery of a variety of small molecule LHR and FSHR agonists and antagonists, some of which have shown highly promising efficacy in animal models of fertility control.

Keywords::

• agonist
• antagonist
• contraception
• follicle-stimulating hormone (FSH)
• FSHR
• infertility
• luteinising hormone (LH)
• LHR