Yonsei Med J.  1994 Dec;35(4):493-501. 10.3349/ymj.1994.35.4.493.

Effect of adenylate cyclase inhibitor and protein kinase C inhibitor on GnRH-induced LH release and LH beta subunit biosynthesis in rat anterior pituitary cells

• Kim C
• Park D
• Ryu K

• KMID: 1125988
• DOI: http://doi.org/10.3349/ymj.1994.35.4.493

Abstract

According to our previous studies together with others, GnRH, a hypothalamic decapeptide, has been known to be a major regulator for LH release and its subunit biosynthesis in anterior pituitary gonadotropes. But the precise mechanisms by which GnRH exerts stimulatory effects on LH release and its subunit biosynthesis have not been clearly understood. In the present study we examined the effect of GnRH on protein kinase C (PKC) activity and intracellular cAMP content in cultured anterior pituitary cells of rat to clarify whether PKC or cAMP are involved in GnRH action. Moreover, we examined the effects of staurosporine (ST), a PKC inhibitor and 2',3'-dideoxyadenosine (2',3'-DDA), an adenylate cyclase inhibitor, on LH release and steady state LH beta subunit mRNA levels in cultured anterior pituitary cells of rat. PKC activity was rapidly increased within 30 min after GnRH treatment whereas intracellular cAMP level was elevated 18 h after GnRH treatment. ST significantly inhibited GnRH-induced LH release and LH beta subunit mRNA levels in a dose-dependent manner, showing an half maximal response at 50 nM ST. 2',3'-DDA inhibited GnRH-induced LH release and LH beta subunit mRNA levels in a dose-dependent manner in pituitary cells. From these results, it is suggested that GnRH stimulates LH beta subunit mRNA level as well as LH release in anterior pituitary cells and this GnRH action might be mediated by PKC activation and cAMP stimulation.

Keyword

GnRH; LH; staurosporine; 2'; 3'-dideoxyadenosine; protein kinase C; cAMP; pituitary cells

MeSH Terms

Adenylate Cyclase/*antagonists & inhibitors
Alkaloids/*pharmacology
Animal
Cells, Cultured
Cyclic AMP/metabolism
Dideoxyadenosine/*pharmacology
Female
Gonadorelin/*pharmacology
Luteinizing Hormone/*biosynthesis/*metabolism
Pituitary Gland, Anterior/*drug effects/metabolism
Protein Kinase C/*antagonists & inhibitors/metabolism
Rats
Rats, Sprague-Dawley
Staurosporine
Support, Non-U.S. Gov't