Abstract
The glycoprotein hormones (GPH) are heterodimers composed of a common α subunit and a specific β subunit. They act by activating specific leucine-rich repeat G protein-coupled receptors. However, individual subunits have been shown to elicit responses in cells devoid of the receptor for the dimeric hormones. The α subunit is involved in prolactin production from different tissues. The human chorionic gonadotropin β subunit (βhCG) plays determinant roles in placentation and in cancer development and metastasis. A truncated form of the thyrotropin (TSH) β subunit is also reported to have biological effects. The GPH α- and β subunits are derived from precursor genes (gpa and gpb, respectively), which are expressed in most invertebrate species and are still represented in vertebrates as GPH subunit paralogs (gpa2 and gpb5, respectively). No specific receptor has been found for the vertebrate GPA2 and GPB5 even if their heterodimeric form is able to activate the TSH receptor in mammals. Interestingly, GPA and GPB are phylogenetically and structurally related to cysteine-knot growth factors (CKGF) and particularly to a group of antagonists that act independently on any receptor. This review article summarizes the observed actions of individual GPH subunits and presents the current hypotheses of how these actions might be induced. New approaches are also proposed in light of the evolutionary relatedness with antagonists of the CKGF family of proteins.
Highlights
The glycoprotein hormones (GPH) are heterodimers composed of a common a subunit and a specific b subunit
The vertebrate forms of these precursor genes where first characterized in human [67] so that they were named gpa2 or gpha2, i.e. GPH a subunit type 2-encoding gene and gpb5 or gphb5, i.e. GPHb subunit type 5 encoding gene (LHb, FSHb, TSHb and CGb subunits counting for types 14)
GPHs luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) are restricted to vertebrates, a gphr related (LGR-1, a type A LGR) gene was identified in several non-vertebrate groups [81, 83, 84] that arose with the emergence of bilaterians [68]
Summary
The glycoprotein hormones (GPH) are heterodimeric glycoproteins composed of an a subunit that is common to all of them and a b subunit that confers the hormonal specificity to the dimer. The hypothalamus provides the main activators of the GPHs production These stimulators are short peptides produced by specific neurons that are delivered by pulses into the blood that irrigates the anterior pituitary gland. The gonadotropin-releasing hormone (GnRH) preferentially stimulates the production of lhb or fshb subunit genes according to pulse amplitude and frequency [25]. Other gonadal (inhibin, activin), metabolic (leptin, fatty acids) or paracrine and autocrine factors contribute to the fine-tuning of LH or FSH production and secretion Both PD-TSH a and b subunits are stimulated by the thyrotropin-releasing hormone (TRH) in mammals [28, 29] or corticotropin-releasing hormone (CRH) in most nonmammalian vertebrates [30]. Numerous paracrine and autocrine factors participate to achieve an appropriate TH circulating level [32]
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