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Review
doi: 10.12703/r/10-41. eCollection 2021.

Recent advances in understanding gonadotropin signaling

Affiliations
Review

Recent advances in understanding gonadotropin signaling

Livio Casarini et al. Fac Rev..

Abstract

Gonadotropins are glycoprotein sex hormones regulating development and reproduction and bind to specific G protein-coupled receptors expressed in the gonads. Their effects on multiple signaling cascades and intracellular events have recently been characterized using novel technological and scientific tools. The impact of allosteric modulators on gonadotropin signaling, the role of sugars linked to the hormone backbone, the detection of endosomal compartments supporting signaling modules, and the dissection of different effects mediated by these molecules are areas that have advanced significantly in the last decade. The classic view providing the exclusive activation of the cAMP/protein kinase A (PKA) and the steroidogenic pathway by these hormones has been expanded with the addition of novel signaling cascades as determined by high-resolution imaging techniques. These new findings provided new potential therapeutic applications. Despite these improvements, unanswered issues of gonadotropin physiology, such as the intrinsic pro-apoptotic potential to these hormones, the existence of receptors assembled as heteromers, and their expression in extragonadal tissues, remain to be studied. Elucidating these issues is a challenge for future research.

Keywords: FSH; FSHR; LH; LHCGR; allosteric modulator; endosome; gonadotropin; hCG; reproduction; signaling.

Copyright: © 2021 Simoni M et al.

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Conflict of interest statement

The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Endosomal signaling of gonadotropin receptors.
Receptor bound to the hormone is internalized via different kinds of endosomal compartments, sustaining prolonged signaling, receptor degradation, or recycling on the cell surface. AKT, protein kinase B; ERK1/2, extracellular-regulated kinase 1 and 2; GIPC, “Gαi-interacting protein C-terminus”; RAB4, Ras-related protein Rab-4; RAB5, Ras-related protein Rab-5; RAB7, Ras-related protein Rab-7.
Figure 2.
Figure 2.. LH- and hCG-specific signals.
LH and hCG induce different intracellular signaling. Whereas LH is more potent than hCG in activating proliferative and survival signals via EK1/2 and AKT phosphorylation, the choriogonadotropin acts preferentially as a progestational, inducing a more potent cAMP response. H-hCG has a relatively high proliferative potential and lower activity than hCG in activating the receptor. AKT, protein kinase B; ERK1/2, extracellular-regulated kinase 1 and 2; hCG, human chorionic gonadotropin; H-hCG, hyperglycosylated human chorionic gonadotropin; LH, luteinizing hormone; LHCGR, luteinizing hormone/chorionic gonadotropin receptor.
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This work was supported by a “Departments of Excellence Programme” grant from the Italian Ministry for Education, University and Research to the Department of Biomedical, Metabolic and Neural Sciences (University of Modena and Reggio Emilia).

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