Expression of steroidogenic acute regulatory protein in the human corpus luteum throughout the luteal phase

The expression of the steroidogenic acute regulatory protein (StAR) in the human corpus luteum (CL) was examined throughout the luteal phase. The prim ary 1.6-kb SCAR transcript was in greater abundance in early (3.1-fold) and mid (2.2-fold) luteal phase CL compared with late luteal phase CL. The lar ger StAR transcript (4.4 kb) was found in early and midluteal phase CL, but was not detected in late luteal phase specimens. Mature StAR protein (30 k Da) was present in lower amounts within late CL compared with early and mid luteal phase CL. The StAR preprotein (37 kDa) was also detected in greater abundance in early and midluteal CL. Immunohistochemistry revealed that StA R staining was most prominent in thecal-lutein cells throughout the luteal phase. The intensity of the signal for StAR exhibited significant changes t hroughout the luteal phase, being most intense during the midluteal phase a nd least during the late luteal phase. Plasma progesterone concentrations w ere highly correlated (r = 0.73 and r = 0.79) with luteal expression of the preprotein and mature StAR isoforms, respectively, throughout the luteal p hase. To examine the LH dependency of SCAR expression, the GnRH antagonist, Cetrorelix, was administered during the midluteal phase. Cetrorelix caused a decline in serum LH levels within 2 h, which, in turn, caused a pronounc ed decline in plasma progesterone within 6 h. The StAR 4.4-kb transcript wa s not detectable, and the 1.6-kb transcript was reduced by approximately 50 % within 24 h of Cetrorelix treatment. The mature 30-kDa StAR protein level declined approximately 30% after Cetrorelix treatment. We conclude that 1) StAR mRNA and protein are highly expressed in early and midluteal phase CL ; 2) StAR protein is present in both thecal-lutein and granulosa-lutein cel ls throughout the luteal phase; 3) StAR protein levels in the CL are highly correlated with plasma progesterone levels; 4) declining StAR mRNA and pro tein levels are characteristic of late luteal phase CL; and 5) suppression of LH levels during the midluteal phase results in a marked decline in plas ma progesterone and a diminished abundance of StAR transcripts in the CL wi thout a corresponding significant decline in StAR protein. Collectively, th ese data are consistent with the idea that StAR gene expression is a key de terminant of luteal progesterone during the normal menstrual cycle. However , the pharmacologically induced withdrawal in the midluteal phase of LH sup port diminishes luteal progesterone output by mechanisms others than reduce d SCAR protein levels: