Enhanced follicle-stimulating hormone activity of deglycosylated human chorionic gonadotropin in ovarian granulosa cells.
The receptor binding properties and biological actions of chemically deglycosylated asialo human CG (AHF-hCG) were studied in ovarian granulosa cells from diethylstilbestrol (DES)-treated immature rats. In ovarian homogenates from DES- and FSH-treated rats, the relative binding affinity of AHF-hCG was 2-fold higher than that of native hCG and 14-fold higher than that of ovine LH. When assayed for LH-like activity in granulosa cells from DES plus FSH-treated animals, the deglycosylated hormone behaved as a partial agonist in terms of cAMP formation, but fully stimulated progesterone production to the same extent as that elicited by LH. When added with LH to FSH-treated cells, AHF-hCG inhibited LH-stimulated cAMP formation by 70% but did not alter the elevated level of progesterone production. These findings are consistent with the presence of excess or spare LH receptors in the maturing granulosa cell. When added to freshly prepared granulosa cells which have minimal LH receptors, AHF-hCG decreased FSH-stimulated cAMP production by 20% and reduced progesterone production by 50% and increased cGMP formation by 100% during 48 h of culture. The ability of AHF-hCG to decrease the progesterone response to FSH suggests that no spare FSH receptors are present during granulosa cell differentiation. In contrast, native hCG did not alter FSH-induced cAMP or progesterone production but reduced the cGMP responses to FSH and choleragen. Whereas native hCG displayed negligible binding potency when compared with that of ovine FSH in competition with [125I]iodo-human FSH for ovarian receptors, AHF-hCG bound to FSH receptors with about 5% of the binding affinity of ovine FSH. In choleragen-treated granulosa cells, the increases in cAMP and progesterone synthesis were enhanced by addition of both hCG and AHF-hCG, and cGMP production was increased by AHF-hCG but slightly decreased by hCG. These results indicate that the enhanced LH receptor affinity caused by removal of the sugar moieties from hCG is accompanied by a relatively greater increase in FSH receptor affinity, and that deglycosylated hCG acts as a partial agonist with the ability to modify granulosa cell responses to both LH and FSH.
Ranta
T
T
Chen
H C
HC
Shimohigashi
Y
Y
Baukal
A J
AJ
Knecht
M
M
Catt
K J
KJ
D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004054:Diethylstilbestrol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011962:Receptors, FSH; D011974:Receptors, LH; D013329:Structure-Activity Relationship
D006063:Chorionic Gonadotropin; C034923:HCG, deglycosylated; D011956:Receptors, Cell Surface; D011962:Receptors, FSH; D011974:Receptors, LH; D011374:Progesterone; D004054:Diethylstilbestrol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D006152:Cyclic GMP