FSH mediated cAMP signalling upregulates the expression of Gα subunits in pubertal rat Sertoli cells

Biochem Biophys Res Commun. 2021 Sep 10:569:100-105. doi: 10.1016/j.bbrc.2021.06.094. Epub 2021 Jul 5.

Abstract

Follicle Stimulating Hormone (FSH) acts via FSH-Receptor (FSH-R) by employing cAMP as the dominant secondary messenger in testicular Sertoli cells (Sc) to support spermatogenesis. Binding of FSH to FSH-R, results the recruitment of the intracellular GTP binding proteins, either stimulatory Gαs or inhibitory Gαi that in turn regulate cAMP production in Sc. The cytosolic concentration of cAMP being generated by FSH-R thereafter critically determines the downstream fate of the FSH signalling. The pleiotropic action of FSH due to differential cAMP output during functional maturation of Sc has been well studied. However, the developmental and cellular regulation of the Gα proteins associated with FSH-R is poorly understood in Sc. In the present study, we report the differential transcriptional modulation of the Gα subunit genes by FSH mediated cAMP signalling in neonatal and pubertal rat Sc. Our data suggested that unlike in neonatal Sc, both the basal and FSH/forskolin induced expression of Gαs, Gαi-1, Gαi-2 and Gαi-3 transcripts was significantly (p < 0.05) up-regulated in pubertal Sc. Further investigations involving treatment of Sc with selective Gαi inhibitor pertussis toxin, confirmed the elevated expression of Gi subunits in pubertal Sc. Collectively our results indicated that the high level of Gαi subunits serves as a negative regulator to optimize cAMP production in pubertal Sc.

Keywords: Adenyly cyclase; FSH; G-protein; Sertoli cell; cAMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Follicle Stimulating Hormone / metabolism
  • Follicle Stimulating Hormone / pharmacology*
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Gene Expression Regulation / drug effects
  • Male
  • Pertussis Toxin / pharmacology
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Receptors, FSH / genetics
  • Receptors, FSH / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism
  • Sexual Maturation / physiology
  • Signal Transduction / drug effects*
  • Spermatogenesis / drug effects
  • Spermatogenesis / genetics

Substances

  • Receptors, FSH
  • Colforsin
  • Follicle Stimulating Hormone
  • Cyclic AMP
  • Pertussis Toxin
  • GTP-Binding Protein alpha Subunits, Gi-Go