Luteinizing hormone (LH) and chorionic gonadotropin (CG) are glycoproteins fundamental for sexual development and reproduction. Since they act on the same receptor (LHCGR), there is a general consensus that LH and hCG are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ∼85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in a ∼90 min half-life molecule targeting the gonads, to regulate gametogenesis and androgen synthesis. Trophoblast hCG, the "pregnancy hormone", exists in several isoforms and glycosylation variants with long half-lives (hours), angiogenic potential, and acts on luteinized ovarian cells as a progestational. The different molecular features of LH and hCG lead to hormone-specific LHCGR binding and intracellular signaling cascades. In ovarian cells, LH action is preferentially exerted through kinases, pERK1/2 and pAKT, resulting in irreplaceable proliferative/anti-apoptotic signals and partial agonism on progesterone production in vitro. In contrast, hCG displays notable cAMP/PKA-mediated steroidogenic and pro-apoptotic potential, which is masked by estrogen action in vivo. In vitro data are confirmed by large dataset from assisted reproduction, since the steroidogenic potential of hCG positively impacts on the number of retrieved oocytes, while LH impacts pregnancy rate (per oocyte number). Interestingly, Leydig cell in vitro exposure to hCG results in qualitatively similar cAMP/PKA and pERK1/2 activation as compared to LH, as well as testosterone. The supposed equivalence of LH and hCG is debunked by such data highlighting their sex-specific functions, thus deeming it an oversight caused by incomplete understanding of clinical data.

Two hormones for one receptor: evolution, biochemistry, actions and pathophysiology of LH and hCG / Casarini, Livio; Santi, Daniele; Brigante, Giulia; Simoni, Manuela. - In: ENDOCRINE REVIEWS. - ISSN 0163-769X. - 39:5(2018), pp. 549-592. [10.1210/er.2018-00065]

Two hormones for one receptor: evolution, biochemistry, actions and pathophysiology of LH and hCG

Casarini, Livio;Santi, Daniele;Brigante, Giulia;Simoni, Manuela
2018

Abstract

Luteinizing hormone (LH) and chorionic gonadotropin (CG) are glycoproteins fundamental for sexual development and reproduction. Since they act on the same receptor (LHCGR), there is a general consensus that LH and hCG are equivalent. However, separate evolution of LHβ and hCGβ subunits occurred in primates, resulting in two molecules sharing ∼85% identity and regulating different physiological events. Pituitary, pulsatile LH production results in a ∼90 min half-life molecule targeting the gonads, to regulate gametogenesis and androgen synthesis. Trophoblast hCG, the "pregnancy hormone", exists in several isoforms and glycosylation variants with long half-lives (hours), angiogenic potential, and acts on luteinized ovarian cells as a progestational. The different molecular features of LH and hCG lead to hormone-specific LHCGR binding and intracellular signaling cascades. In ovarian cells, LH action is preferentially exerted through kinases, pERK1/2 and pAKT, resulting in irreplaceable proliferative/anti-apoptotic signals and partial agonism on progesterone production in vitro. In contrast, hCG displays notable cAMP/PKA-mediated steroidogenic and pro-apoptotic potential, which is masked by estrogen action in vivo. In vitro data are confirmed by large dataset from assisted reproduction, since the steroidogenic potential of hCG positively impacts on the number of retrieved oocytes, while LH impacts pregnancy rate (per oocyte number). Interestingly, Leydig cell in vitro exposure to hCG results in qualitatively similar cAMP/PKA and pERK1/2 activation as compared to LH, as well as testosterone. The supposed equivalence of LH and hCG is debunked by such data highlighting their sex-specific functions, thus deeming it an oversight caused by incomplete understanding of clinical data.
2018
39
5
549
592
Two hormones for one receptor: evolution, biochemistry, actions and pathophysiology of LH and hCG / Casarini, Livio; Santi, Daniele; Brigante, Giulia; Simoni, Manuela. - In: ENDOCRINE REVIEWS. - ISSN 0163-769X. - 39:5(2018), pp. 549-592. [10.1210/er.2018-00065]
Casarini, Livio; Santi, Daniele; Brigante, Giulia; Simoni, Manuela
File in questo prodotto:
File Dimensione Formato  
Casarini_Endocr reviews_2018.pdf

Open access

Descrizione: Articolo principale
Tipologia: Versione pubblicata dall'editore
Dimensione 5.54 MB
Formato Adobe PDF
5.54 MB Adobe PDF Visualizza/Apri
Casarini_Endocr reviews_2018_invited.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 5.62 MB
Formato Adobe PDF
5.62 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1164248
Citazioni
  • ???jsp.display-item.citation.pmc??? 42
  • Scopus 105
  • ???jsp.display-item.citation.isi??? 98
social impact