Mechanism of action of gonadotropin-releasing hormone upon gonadotropin α-subunit mRNA levels in the αT3-1 cell line: Role of Ca2+ and protein kinase C

D. Ben-Menahem, Z. Shraga-Levine, P. L. Mellon, Z. Naor

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Abstract

Addition of [D-Trp6]gonadotropin-releasing hormone (GnRHa) to αT3-1 cells induced a very rapid response upon gonadotropin α-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 α-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 α-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 extracellular Ca2+ abolished the effect of GnRHa and PMA upon α-subunit mRNA levels. Interestingly PMA and ionomycin had no effect on α-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 α-subunit mRNA elevation and that differential cross-talk exists between the messengers.

Original languageEnglish
Pages (from-to)325-329
Number of pages5
JournalBiochemical Journal
Volume309
Issue number1
DOIs
StatePublished - 1 Jan 1995
Externally publishedYes

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