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**111**

**Chapter 7**

**Abstract**

The Low-Molecular-Weight

of the Regulators of the

*Alexander O. Shpakov, Kira V. Derkach,* 

*Andrey A. Bakhtyukov and Dmitry V. Dar'in*

Steroidogenesis

use in reproductive medicine.

**1. Introduction**

Ligands of the Gonadotropin

Reproductive Functions and

Receptors as the New Generation

In clinic, the luteinizing (LH) and follicle-stimulating (FSH) hormones and human chorionic gonadotropin (hCG) are used to treat reproductive dysfunctions and in assisted reproductive technology. They are the αβ-heterodimeric complexes and specifically bind to ectodomain of G protein-coupled LH and FSH receptors. This leads to activation of many signaling cascades; some of which are responsible for steroidogenesis, folliculogenesis, and spermatogenesis, while the others, such as β-arrestin pathways, trigger the downregulation of gonadotropin receptors. A low selectivity of the intracellular signaling of gonadotropins and a large number of their isoforms are the main causes of undesirable effects of gonadotropins, limiting their clinical applications. Unlike gonadotropins, the low-molecular-weight (LMW) ligands interact with an allosteric site located in the transmembrane domain of the LH and FSH receptors and selectively activate the certain signaling pathway, preventing a number of side effects of gonadotropins. The LMW ligands are characterized by activity of the full and inverse agonists and neutral antagonists, as well as the positive and negative modulators, and they have the in vivo activity, including when administered orally. This review focuses on the advances in the development of LMW allosteric ligands of the LH and FSH receptors and the prospects for their

**Keywords:** sex steroid hormone, steroidogenesis, low-molecular-weight agonist, luteinizing hormone, follicle-stimulating hormone, receptor of luteinizing hormone

The most important areas of clinical applications of the gonadotropins, such as the luteinizing (LH) and follicle-stimulating (FSH) hormones and human chorionic gonadotropin (hCG), are (i) the stimulation of the steroidogenesis,
