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International audience; The thyroid-stimulating hormone receptor (TSHR), luteinizing hormone receptor (LHCGR), and follicle-stimulating hormone receptor (FSHR) are collectively referred to as the glycoprotein hormone receptors because they bind structurally similar glycoprotein hormones. The glycoprotein hormones consist of the pituitary thyroid-stimulating hormone (thyrotropin, TSH), luteinizing hormone (lutropin, LH), and follicle-stimulating hormone (follitropin, FSH) as well as the chorionic gonadotropin (choriogonadotropin, CG) placental hormone. The glycoprotein hormones are each composed of two dissimilar subunits (α and β) that are noncovalently associated. Within a given species, the α-subunit is identical and the β-subunits are distinct but homologous. Due to the largely similar nature of LHβ and CGβ, the LHCGR binds either LH or CG. The binding specificity of LH/CG to the LHCGR, FSH to the FSHR, and TSH to the TSHR is fairly strict. However, in some cases, extremely high levels of hormone can cause activation of the inappropriate receptor. Because the LHCGR and FSHR are localized primarily to the gonads, these two receptors are also referred to as the gonadotropin receptors. The glycoprotein hormone receptors belong to the family A (rhodopsin-like) of G protein-coupled receptors (GPCRs). However, they share the relatively unique feature of having a large extracellular domain that mediates high affinity binding of the hormone. In spite of their different physiological roles, the glycoprotein hormone receptors share a similar structural organization and mechanism of action.

The gonads (ovary, testis) produce gametes (oocytes and spermatozoa). The pituitary glycoprotein hormones luteinizing hormone (LH, lutropin) and follicle-stimulating hormone (FSH, follitropin) are gonadotropins because their targets are the gonads. Another hormone produced by the syncytiotrophoblast of the human placenta is human chorionic gonadotropin (hCG, choriogonadotropin), and its activity is like LH. This review describes the protein structure, gene structure, and regulation of biosynthesis of both the gonadotropins and their membrane bound receptors. The functions of both hormones and receptors are covered extensively, as well as naturally occurring mutations that have been identified in disease states and therapies derived from their study.

Objective To highlight the clinical role of standard GH replacement treatment on fertility and pregnancy outcomes in four infertile eugonadal women with GH deficiency (GHD). Design Case report. Setting Department of endocrinology and infertility clinic, tertiary-care university hospital. Patient(s) Four normogonadotrophic, normoprolactinemic patients with long-standing infertility, affected by GHD. In two patients (aged 30 and 34 years) GHD was diagnosed after a brain injury. The third patient (age 30 years) had a primary empty sella, documented by magnetic resonance imaging of the pituitary. The last patient (age 28 years) underwent transsphenoidal surgery for Ratke's cyst. The LH and FSH responses to GnRH were normal in all four patients. Two of the four patients also had secondary hypoadrenalism and hypothyroidism. Intervention(s) Patients received recombinant human GH replacement therapy (0.9–1.8 mg/week) for 6–12 months until pregnancy was first indicated by biochemical markers (β-hCG) and later confirmed by transvaginal sonography. The GH therapy was discontinued after confirmation of pregnancy. Main Outcome Measure(s) Pregnancy. Result(s) All patients remained off treatment throughout pregnancy; they had uneventful pregnancies and term deliveries. The babies were healthy and normal in terms of length and weight. Conclusion(s) Our case studies confirm the important clinical role of the GH–insulin-like growth factor I system in oocyte fertilization and the beginning of pregnancy in a selected population of eugonadotrophic infertile women.

Follitropin and the follitropin receptor are essential for normal gamete development in males and females. This review discusses the molecular genetics and structural and cellular biology of the follitropin/follitropin receptor system. Emphasis is placed on the human molecules when possible. The structure and regulation of the genes for the follitropin beta subunit and the follitropin receptor is discussed. Control of systemic and cellular protein levels is explained. The structural biology of each protein is described, including protein structure, motifs, and activity relationships. Finally, the follitropin/follitropin receptor signal transduction system is discussed.

Publisher Summary The molecular cloning of the three glycoprotein hormone receptors in mammals during the past four years has opened a new area in their study. Although the biological effects of these hormones have been known for years, the scarcity of their receptors had, up to now, largely hampered the obtaining of unequivocal results concerning their structure and their transduction mechanism. However, because of their high affinity for the hormone, luteinizing hormone (or lutropin) (LH) and follicle stimulating hormone (or follitropin) (FSH) receptors were detected and quantified relatively easily with radiolabeled tracers and their main second hormonal messenger identified as cyclic AMP. This chapter attempts to survey the recent contributions, which give molecular supports to biological functions of the glycoprotein hormone receptors. As the presence of these receptors on their target organs is essential for the control of reproduction and growth in vertebrates, new insights into the regulation of their expression are also included in this chapter.

Publisher Summary This chapter discusses the structure and function of the carbohydrate chains of the glycoprotein hormone family. The family of glycoprotein hormones consists of lutropin (LH), follitropin (FSH), and thyrotropin (TSH) synthesized in the anterior pituitary and chorionic gonadotropin which is synthesized only in the placenta of human, primate, and equine. The hormones are heterodimers composed of two non-covalently joined α and β subunits. Both subunits are glycosylated and contain N- and, in the case of the CGβ subunit, O-linked oligosaccharides which account for 15-40% of their mass. Assembly of the common α subunit, with any of the four β subunits, results in unique properties of each hormone that are reflected in binding to hormone-specific receptors and subsequent signal transduction. Gonadotropins regulate reproductive functions; LH stimulates steroidogenesis in ovarian granulosa and theca cells, and testicular Leydig cells. One function of hCG is to maintain high progesterone production in the corpus luteum to maintain pregnancy and hCG and LH bind to the same receptor.

Publisher Summary This chapter explains the FHS binding to testes and to study testicular receptors for gonadotropins, it is essential to identify the maturational status of the tissue as key differences can be seen in the biochemical properties and hormone sensitivity of testes from mature compared to immature rats. However, these distinctions relate mainly to adenylyl cyclase and protein kinase activities but most biochemical processes and hormonal responses of rat testes depends on the age and the most distinct one is in immature testes, which then declines after almost 21 days. Furthermore, testes from mature rats were chosen as the receptor source purposefully as noteworthy distinctions were present in the characteristics of the hormone-receptor interaction and factors influencing it in testes from mature rats as compared to the immature once, as well as among receptors in testes from different species.