Ovarian Cyclic Adenosine Monophosphate-Dependent Protein Kinase Activity: Ontogeny and Effect of Gonadotropins

Abstract

The ontogeny of ovarian cyclic AMP-binding and protein kinase activities during the postnatal development of the rat, as well as the effect of LH and FSH administration on ovarian cyclic AMP-binding and protein kinase activities in 5-day-old and in hypophysectomized rats was examined. Ovaries of 4 to 8-day-old rats possessed little or no measureable cyclic AMP-binding and protein kinase activities. Subsequent postnatal development occurred in three distinct phases. During the first phase, ovarian cyclic AMP-binding and protein kinase activities increased progressively from age 8 days to age 23 days, when adult levels were observed. Protein kinase activity declined markedly during the second postnatal developmental phase from days 24 to 26, lost its cyclic AMP-dependency, and became refractory to stimulation by cyclic AMP. Studies employing a heat-stable protein kinase inhibitor protein isolated from rabbit skeletal muscle suggest that ovarian protein kinase activity during the refractory period was largely of the cyclic AMP-independent variety. During the third postnatal phase, comprising days 30 to 40, ovarian cyclic AMP-binding and protein kinase activities increased to levels seen in sexually mature rats. Protein kinase cyclic AMP-dependency which was lost during the refractory second postnatal period was fully restored during the third phase. Administration of FSH or LH led to a marked increase of ovarian cyclic AMP-binding and protein kinase activities in 5-day-old rats. Hypophysectomy of 20-day-old rats caused a significant reduction of the cyclic AMP-binding and protein kinase activities in a 27,000 X g supernatant fraction, as well as in the mitochondrial, microsomal, and 105,000 X g supernatant fraction. The decreased cyclic AMP-binding and protein kinase activities of these fractions could be partially restored by FSH or LH treatment of the hypophysectomized rats. The results indicate that ovarian cyclic AMP-binding and protein kinase activities, as well as the ability of ovarian protein kinase to respond to cyclic AMP are gradually acquired after the first postnatal week. The postnatal development of ovarian protein kinase and cyclic AMP-binding activities presumably involves the participation of FSH and LH, although the precise mechanism of LH and FSH action remains to be established.