Regulation of immunoreactive inhibin A and B secretion in cultured human granulosa-luteal cells by gonadotropins, activin A and insulin-like growth factor type-1 receptor.
Inhibins are gonadal glycoproteins with endocrine effects on pituitary FSH secretion and para/autocrine effects on ovarian and testicular function. The purpose of this study was to investigate the endocrine and para/autocrine regulation of inhibin A and inhibin B secretion in human ovarian granulosa-luteal cells. The cells were obtained from women undergoing in vitro fertilization, and the primary cultures were treated with FSH, LH, human chorionic gonadotropin (hCG), activin A, 8-bromo cyclic AMP (8-BrcAMP), staurosporine (a protein kinase C inhibitor) and an antagonist of IGF action (type-1 IGF receptor antibody alpha IR3). The secretion of inhibins was measured by ELISA assays capable of reliably distinguishing between inhibin A and B. FSH, LH, hCG and 8-BrcAMP increased inhibin A secretion on average up to 180% (P<0.01), 192% (P<0.05), 210% (P<0.01) and 243% (P<0.01) respectively of the control level, while their stimulatory effect on inhibin B secretion was less pronounced (up to 167%, P<0.01; 139%, P<0.05; 127%, P>0.05; 133%, P>0.05 of the controls respectively). alpha IR3 decreased inhibin A and B secretion down to 70% (P<0.01) and 50% (P<0.01) respectively of the control. Staurosporine decreased inhibin B secretion down to 49% (P<0.01) of the control; its effect on inhibin A secretion was not significant. Activin A increased inhibin B secretion up to fourfold of the control (P<0.05) while its effect on inhibin A secretion was insignificant. We conclude that gonadotropins via the protein kinase A signal transduction pathway are the main positive regulators of inhibin A and B secretion in human granulosa-luteal cells. The protein kinase C signal transduction pathway seems to be important especially for inhibin B secretion. Locally produced IGFs are probably important inducers of the production of both forms of inhibin in human ovaries while activins seem to upregulate inhibin B secretion.
Vänttinen
T
T
Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
Liu
J
J
Liu
J
J
Hydén-Granskog
C
C
Parviainen
M
M
Penttilä
I
I
Voutilainen
R
R
D028341:Activins; D018929:Cell Culture Techniques; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000166:cytology / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006062:Gonadotropins / Q000494:pharmacology*; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017526:Receptor, IGF Type 1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C