Changes in expression of adenyl cyclase activity in human endometrium during hormone replacement therapy and ovarian stimulation

We have investigated membrane fractions prepared from human endometrium for activity of the signalling adenyl cyclase (AC). We characterized the AC guanine nucleotide-binding proteins (G proteins) and examined the changes in AC activity during evaluation cycles of oestrogen and progesterone replacement therapy as well during ovarian stimulation cycles. AC activity was determined by the conversion of substrate ATP into cyclic AMP under basal conditions and in the presence of guanine nucleotide or forskolin. G proteins were determined by Western Blot using specific polyclonal antibodies against Gs alpha, Gi1,2 alpha and Gi3 alpha. Our results indicate that endometrial AC was highly responsive to activation by both guanine nucleotide and forskolin and its rate of cyclic AMP production was highly pronounced. Mean activity reached 920 pmol/l/min/mg membrane protein in the presence of forskolin, a value similar to 5-fold higher than those detected in corpus luteum. Hormonal induction of AC activities increased Gs alpha protein, which couples with and stimulates the catalytic component of AC. We conclude that human endometrium is rich in AC and that enzyme activity is induced by oestrogen and progesterone treatment. These data strongly support the concept that the transmembrane signalling AC system and its messenger cyclic AMP are major regulators of endometrial function in the human.