GONADOTROPIN-RELEASING-HORMONE RECEPTOR GENE-EXPRESSION IN HUMAN OVARY AND GRANULOSA-LUTEIN CELLS

GnRH regulates gonadotropin biosynthesis and release in the anterior p ituitary via specific receptors. Although extrapituitary expression an d action of GnRH have been shown in some species, in the human it is n ot clear whether GnRH has a peripheral action. In this study we sought to determine whether the human ovary expresses GnRH receptor (GnRHR) messenger ribonucleic acid (mRNA). Ovarian tissues from 11 women (32-6 1 yr old) and granulosa-lutein (GL) cells purified from follicular asp irates of 51 women undergoing oocyte retrieval for in vitro fertilizat ion were analyzed by ribonuclease protection assay and reverse transcr iptase-polymerase chain reaction (RT-PCR). Human pituitaries, lymphocy tes, and placenta were also studied. Measurable levels of GnRHR mRNA w ere found by ribonuclease protection assay in 2 of 10 ovaries, in 2 of 4 GL cells preparations from women whose ovarian hyperstimulation inv olved a GnRH agonist, in GL cells from 3 women whose ovarian hyperstim ulation involved a GnRH antagonist, and in human pituitaries. Relative to the total amount of RNA analyzed, the level of GnRHR mRNA was abou t 200-fold lower in the ovary than in the pituitary. A sequence of 314 basepairs of GnRHR mRNA was amplified by RT-PCR in the pituitary, in 9 of 10 ovaries, and in 4 of 5 GL cell preparations. No message could be amplified in human lymphocytes, and placental specimens showed a we ak signal. The relative GnRHR mRNA levels in GL cells from 13 women an alyzed by quantitative RT-PCR showed a wide range of individual differ ences. These results suggest that GnRHR mRNA is expressed in GL cells and the human ovary across different functional stages, implying that multiple ovarian compartments may express GnRH receptors. The administ ration of GnRH analogs may have a further direct action on the human o vary.