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New evidence for an acute role of protein kinase in hCG action
Abstract:
The present experiments were designed to study whether exogenous hCG could elicit acute changes in the ovarian concentration of soluble cAMP-dependent protein kinases temporally related to binding of hCG and intracellular accumulation of cAMP. Cyclic AMP dependent protein kinase activity decreased five-fold within 5 to 30 min after intravenous administration of highly purified hCG to pseudopregnant rats. Moreover cAMP dependent protein kinase activity was totally suppressed with 0.5 IU hCG, whereas tissue concentration of cAMP continued to increase throughout the dose range (0.05-5.0 IU) of hCG used in the present studies. A marked fall in cAMP-dependent protein kinase activity had occurred before there was a significant change in intracellular accumulation of cAMP, possibly reflecting intracellular compartmentalization of cAMP. Inhibitors of protein did not affect the hCG-induced changes in tissue concentrations of cAMP and soluble cAMP dependent protein kinase activity but did suppress the recovery of cAMP dependent protein kinase activity to pretreatment levels. Cyclic AMP dependent protein kinases appear to play a significant role in mediating hormonal action in vivo. In addition the present studies suggest that, protein kinases may protect the cell from excessive hormonal stimulation.
Insights
Exogenous human chorionic gonadotropin (hCG) acutely decreases ovarian cAMP-dependent protein kinase activity in rats. This suggests protein kinases mediate hormonal actions and may prevent excessive cellular stimulation.
Area of Science:
- Reproductive Endocrinology
- Molecular Endocrinology
- Cellular Signaling
Background:
- Human chorionic gonadotropin (hCG) is a key hormone in reproduction.
- Cyclic AMP (cAMP) and its dependent protein kinases are crucial intracellular messengers.
- The precise role of cAMP-dependent protein kinases in ovarian response to hCG requires further elucidation.
Purpose of the Study:
- To investigate the acute effects of exogenous hCG on ovarian concentrations of soluble cAMP-dependent protein kinases.
- To determine the temporal relationship between hCG binding, cAMP accumulation, and protein kinase activity changes.
- To explore the role of protein kinases in mediating hCG's hormonal actions in vivo.
Main Methods:
- Administration of purified hCG intravenously to pseudopregnant rats.
- Measurement of soluble cAMP-dependent protein kinase activity in ovarian tissue.
- Quantification of intracellular cAMP concentrations.
- Use of protein kinase inhibitors to assess recovery of enzyme activity.
Main Results:
- A five-fold decrease in cAMP-dependent protein kinase activity was observed within 5-30 minutes post-hCG administration.
- Complete suppression of kinase activity occurred with 0.5 IU hCG, while cAMP levels continued to rise.
- The decline in kinase activity preceded significant cAMP accumulation, suggesting compartmentalization.
- Protein kinase inhibitors did not alter hCG-induced changes but delayed the recovery of kinase activity.
Conclusions:
- Exogenous hCG rapidly modulates ovarian cAMP-dependent protein kinase activity.
- These kinases appear to play a significant role in mediating hCG's hormonal effects in vivo.
- Protein kinases may serve a protective role against excessive hormonal stimulation in ovarian cells.