The prolactin inhibition of follicle-stimulating hormone-induced aromatase activity in cultured rat granulosa cells is in part tyrosine kinase and protein kinase-C dependent.
The inhibitory actions of prolactin on gonadal steroidogenesis have been reported in different species and under a variety of experimental approaches. In this study, the mechanisms of the in-vitro effects of human prolactin (hPRL) on human follicle stimulating hormone (hFSH)-induced aromatase activity were determined using cultured granulosa cells from diethylstilboestrol (DES)-primed immature rats. Human PRL caused a dose-dependent decrease in hFSH-induced 17 beta-oestradiol production, even when cells were cultured in the presence of a cAMP analogue (8-Br-cAMP). These effects of hPRL appeared to be specific, since addition of an anti-rat PRL receptor monoclonal antibody (mAb) mimicked the hPRL inhibitory effect upon steroidogenesis in rat granulosa cells. In order to assess the importance of tyrosine kinase and protein kinase-C activation in the hPRL inhibitory effects upon oestrogen biosynthesis, cells were cultured in the presence of kinase inhibitors. The results showed that addition of genistein or staurosporine (a tyrosine kinase and protein kinase-C antagonist respectively) to cultured granulosa cells resulted in potent inhibition of hPRL actions upon hFSH-induced aromatization in a dose-dependent manner. These observations suggest that tyrosine kinase and protein kinase-C activation are involved in the biochemical events leading to hPRL inhibitory effects at the gonadal level.
Villanueva
L A
LA
Departamento de Biología de la Reproducción, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico.
Méndez
I
I
Ampuero
S
S
Larrea
F
F
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D000242:Cyclic AMP / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000032:analysis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors*; D019833:Genistein; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology; D007529:Isoflavones / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine / Q000494:pharmacology
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007529:Isoflavones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004958:Estradiol; D011388:Prolactin; D005640:Follicle Stimulating Hormone; D019833:Genistein; D000242:Cyclic AMP; D001141:Aromatase; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine