Studies have been carried out to standardize induced luteolysis model systems utilizing female monkeys and pregnant rats. In monkeys, administration of a single injection of GnRH receptor antagonist, Cetrorelix (CET; 150 μg/kg BW s.c.,), on day 7 of the luteal phase led to profound decrease in serum progesterone (P4) concentration within 24 h (3.6 ± 1.1 vs 0.8 ± 0.2 ng/ml before and 24 h post CET, respectively p<0.05), and followed by premature onset of menses 96 h later. It was observed that a single intravenous injection of rhLH 24 h post CET treatment caused rapid stimulation of P4 secretion within 1 h that lasted up to 24 h. To elucidate the molecular mechanisms associated with brisk restoration of P4 levels, corpora lutea were collected from monkeys treated with VEH, CET, CET+PBS and CET+LH treatments for molecular analyses. Expression of StAR, P450scc, LDLR, 3βHSD and aromatase was decreased in CET and CET+1 h LH treated monkeys. In CET+8 h LH treated monkeys, expression of StAR, P450scc and aromatase was higher. Immunoblot analyses of phospho (p) StAR and total StAR indicated decreased pStAR and total StAR levels in CL of CET treated monkeys, but were higher after LH treatment. In pregnant rat studies, repeated injections of CET (150 μg/kg BW) were required to induce luteolysis. Similar to monkey studies, exogenous LH injection for 1 h in CET treated rats increased serum P4 levels. Expression of hmgcr, hmgcs, ldlr, p450ssc decreased, expression of 20α- hsd increased and pStAR expression was marginally higher after LH treatment. These findings provide evidence for a dynamic interplay of transcriptional and post translational changes in expression of luteal genes following endogenous LH inhibition and replacement studies, and the data further suggests resilience of the CL structure to recover quickly from the LH deprived state.
Miya John, Priyanka Samji, Rahaman Khan H, Akshi Vashistha and Medhamurthy Rudraiah