Gonadotropin Hormones and Their Receptors

Narayan, Prema; Ulloa‐Aguirre, Alfredo; Dias, James A.

doi:10.1016/b978-0-323-47912-7.00002-0

Cited by 8 publications

(19 citation statements)

References 646 publications

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“…LHRs are critical to reproduction in both mammalian sexes [ 1 ]. The receptors are mainly present in gonadal cells, including testicular Leydig cells in men [ 2 ] and target cells in the follicle and corpus luteum of the ovary in women.…”

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

“…In human follicles, LHRs are found in the theca, interstitial, and granulosa cells of the follicle [ 3 ]. LHRs have also been identified in a number of non-gonadal cells, including the human uterus and human skin [ 1 ]. In most, if not all cases, the function of LHRs in these tissues is not known.…”

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

“…In the human testis, where LHRs in Leydig cells and FSHRs in Sertoli cells have been identified using immunohistochemistry [ 4 ], LHRs, stimulated by pituitary LH [ 2 , 5 , 6 ], are necessary for sperm maturation. In females, the LHRs are found in theca cells and differentiated granulosa cells in the ovarian follicle and on luteal cells of the corpus luteum [ 1 ]. LHRs expressed in follicular granulosa and theca cells are necessary for the development of the follicle, enhanced steroidogenesis, and ovulation [ 2 , 7 ].…”

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

“…cAMP functions as an important second messenger within cells, activating signaling cascades that lead to hormone-mediated, receptor-specific cellular responses. The mature human LHRs (hLHRs) consist of 699 amino acids with a molecular mass of about 85,000 Da [ 1 , 5 ]. hLHRs are coded by a single copy gene that consists of 11 exons and 10 introns and are located on chromosome 2 p21 near the gene for FSHRs [ 10 ].…”

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

“…hLHRs are coded by a single copy gene that consists of 11 exons and 10 introns and are located on chromosome 2 p21 near the gene for FSHRs [ 10 ]. LHRs are synthesized as a single polypeptide chain that can be divided functionally into three domains [ 1 , 2 , 11 ]. The large N-terminus extracellular domain with 340 amino acids is extensively glycosylated and contains several leucine-rich repeats flanked by cysteine-rich regions and a hinge region.…”

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

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Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors

et al. 2020

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Signal transduction by luteinizing hormone receptors (LHRs) and follicle-stimulating hormone receptors (FSHRs) is essential for the successful reproduction of human beings. Both receptors and the thyroid-stimulating hormone receptor are members of a subset of G-protein coupled receptors (GPCRs) described as the glycoprotein hormone receptors. Their ligands, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a structurally related hormone produced in pregnancy, human chorionic gonadotropin (hCG), are large protein hormones that are extensively glycosylated. Although the primary physiologic functions of these receptors are in ovarian function and maintenance of pregnancy in human females and spermatogenesis in males, there are reports of LHRs or FSHRs involvement in disease processes both in the reproductive system and elsewhere. In this review, we evaluate the aggregation state of the structure of actively signaling LHRs or FSHRs, their functions in reproduction as well as summarizing disease processes related to receptor mutations affecting receptor function or expression in reproductive and non-reproductive tissues. We will also present novel strategies for either increasing or reducing the activity of LHRs signaling. Such approaches to modify signaling by glycoprotein receptors may prove advantageous in treating diseases relating to LHRs or FSHRs function in addition to furthering the identification of new strategies for modulating GPCR signaling.

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Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

Section: Lhr and Fshr Structure And Functionmentioning

confidence: 99%

See 3 more Smart Citations

Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors

et al. 2020

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Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor

Duan

et al. 2022

Computational and Structural Biotechnology Journal

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Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor

Duan

Zhang

et al. 2023

Nat Commun

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Follicle stimulating hormone (FSH) is an essential glycoprotein hormone for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive and active states, with the active structure bound to FSH and an allosteric agonist compound 21 f. The structures of FSHR are similar to other glycoprotein hormone receptors, highlighting a conserved activation mechanism of hormone-induced receptor activation. Compound 21 f formed extensive interactions with the TMD to directly activate FSHR. Importantly, the unique residue H6157.42 in FSHR plays an essential role in determining FSHR selectivity for various allosteric agonists. Together, our structures provide a molecular basis of FSH and small allosteric agonist-mediated FSHR activation, which could inspire the design of FSHR-targeted drugs for the treatment of infertility and controlled ovarian stimulation for in vitro fertilization.

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Gonadotropin Hormones and Their Receptors

Cited by 8 publications

References 646 publications

Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors

Glycoprotein G-protein Coupled Receptors in Disease: Luteinizing Hormone Receptors and Follicle Stimulating Hormone Receptors

Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor

Mechanism of hormone and allosteric agonist mediated activation of follicle stimulating hormone receptor

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