Mechanism of action of gonadotropin-releasing hormone upon gonadotropin alpha-subunit mRNA levels in the alpha T3-1 cell line: role of Ca2+ and protein kinase C

Addition of [D-Trp6]gonadotropin-releasing hormone (GnRHa) to alpha T3-1 cells induced a very rapid response upon gonadotropin alpha-subunit mRNA which was detected after 30-60 min and was abolished by pretreatment with actinomycin D. A similar response was obtained with the protein kinase C (PKC) a...

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Bibliographic Details
Published in:Biochemical journal 1995-07, Vol.309 ( Pt 1) (1), p.325-329
Main Authors: Ben-Menahem, D, Shraga-Levine, Z, Mellon, P L, Naor, Z
Format: Article
Language:English
Subjects:
Calcium - physiology
Cell Line
Glycoprotein Hormones, alpha Subunit - genetics
Gonadotropin-Releasing Hormone - physiology
Ionomycin - pharmacology
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tetradecanoylphorbol Acetate - pharmacology
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Summary:Addition of [D-Trp6]gonadotropin-releasing hormone (GnRHa) to alpha T3-1 cells induced a very rapid response upon gonadotropin alpha-subunit mRNA which was detected after 30-60 min and was abolished by pretreatment with actinomycin D. A similar response was obtained with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA), or the Ca2+ ionophore, ionomycin. GnRHa (10 nM) also stimulated a secondary rise in alpha-subunit mRNA levels between 12 and 24 h of incubation. No additivity was obtained (at 60 min) upon the combined addition of GnRHa and PMA, GnRHa and ionomycin, or PMA and ionomycin. The effect of GnRHa upon alpha-subunit mRNA was blocked by the PKC inhibitors staurosporine or GF 109203X. Down-regulation of endogenous PKC activity resulted in inhibition of the stimulatory effect of gonadotropin-releasing hormone (GnRH), PMA and ionomycin. Removal of extra-cellular Ca2+ abolished the effect of GnRHa and PMA upon alpha-subunit mRNA levels. Interestingly PMA and ionomycin had no effect on alpha-subunit mRNA levels at 24 h of incubation; however, the combined addition of the drugs mimicked the late phase of GnRHa (10 nM) action. The data provide evidence that PKC and Ca2+ are involved in mediating the early and the late responses of GnRHa upon alpha-subunit mRNA elevation and that differential cross-talk exists between the messengers.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3090325