A comparative study of adenylate cyclase activity and progesterone synthesis in ovine corpora lutea stimulated by different chemical derivatives or natural analogs of ovine LH.
The adenylate cyclase activation by ovine native LH, natural analogs (porcine LH, hCG) and chemical derivatives of LH (methylated, ethylated, isopropylated, guanidinated) was studied in purified plasma membranes of ovine corpora lutea, including the regulatory effects of guanyl 5'-yl imidophosphate (Gpp(NH)p) and Mg2+. The Ka app. for native LH (about 15 nM) was independent of Gpp(NH)p and Mg2+. Similar maximal activation of the enzyme was obtained by using ovine LH or natural analogs, but differences were remarked concerning the Ka app. values of these hormones. Porcine LH was equipotent with ovine LH; on the contrary, hCG exhibited a lower Ka app. value (3 nM). All chemical derivatives (Me-LH, Et-LH, Iso-LH and Gu-LH) exhibited Ka app. higher than native (about 2- to 4-fold), but similar maximal activation. No modification was observed in the regulatory effects of Gpp(NH)p and Mg2+ on the adenylate cyclase activation as a consequence of structural modifications of the hormone. A comparison of the steroidogenic activity on intact luteal cells and the adenylate cyclase activation ability on purified plasma membranes of the derivatives mentioned above evidenced some interesting discrepancies. The drop in adenylate cyclase activation potency of Me-LH was not reflected in its steroidogenic activity (Me-LH was equipotent with native LH); on the contrary, the capacity of Gu-LH to stimulate adenylate cyclase was not so much decreased as was its steroidogenic potency which was almost abolished.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D012756:Sheep
D006063:Chorionic Gonadotropin; D006165:Guanylyl Imidodiphosphate; D011374:Progesterone; D007986:Luteinizing Hormone; D000262:Adenylyl Cyclases; D008274:Magnesium