Endocrine Abstracts (2006) 11 P686

Expressions of KISS1 and GPR54 are differentially regulated by estradiol and GnRH in adult female rat pituitary

N Richard1, G Galmiche2, S Corvaisier1 & ML Kottler1

1Dpt Genetics and Reproduction, Caen, France; 2EA 2608-USC INRA, Caen, France.

Expressions of KISS-1 and GPR54 have been demonstrated in a variety of tissues, including pituitary. Given their role in reproduction and in gonadotrophin secretion, we examined the regulation of their expression by steroids and GnRH in the rat pituitary using real-time PCR procedure.

After ovariectomy (OVX), pituitary KISS-1 mRNA levels dramatically decrease whereas GPR54 transcripts slightly increase compared with intact cycling rats in metestrus. These variations are reverted in vivo by E2 replacement. In addition, activation of ERα by the selective ligand PPT mimics this effect. By contrast, activation of ERβ by the selective ligand DPN does not stimulate KISS1 expression while it suppresses the ovariectomy-induced increase of GPR54 mRNAs.

E2 acts on the hypothalamus and the pituitary gland. Indeed, ovariectomy increases and estradiol replacement restrains, both GnRH pulse frequency and amplitude. To determine whether estradiol acts on the pituitary directly or indirectly via hypothalamic GnRH secretion, OVX rats were treated with a GnRH antagonist or GnRH antagonist plus estradiol. GnRH antagonist administration results in a slight decrease in both KISS1 and GPR54 mRNAs suggesting that GnRH stimulates both KISS1 and GPR54 expression. When E2 was added, KISS1 transcripts increased while that of GPR54 decreased, demonstrating that estradiol acted also at the pituitary level. However, the result observed for KISS1 is conflicting with that observed after ovariectomy, a condition in which hypothalamic GnRH secretion was increased. Taken together, these data suggest that results observed under GnRH antagonist are related on estrogen deprivation.

In conclusion, we clearly demonstrated that KISS1 and its cognate receptor GPR54 are expressed in the pituitary. Estrogens have a main role on the regulation of KISS1 gene expression via ERα signalling pathway. GPR54 expression is regulated by estradiol and GnRH in a manner which appears to parallel that of LHβ.

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