Gonadotropin-releasing hormone/gonadotropin-releasing hormone receptor signaling in the placenta.
OBJECTIVE
This review summarizes our current understanding of the role of gonadotropin-releasing hormone (GnRH)/GnRH receptor (GnRHR) signaling at the maternal-fetal interface.


RESULTS
Several isoforms of GnRH and GnRHR are described. The hypothalamic decapeptide, GnRH-I, binds to the anterior pituitary and induces the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. It is also found in extrahypothalamic sites. A second isoform, GnRH-II, acts both in the hypothalamus and other organ systems, including placenta, breast, endometrium, and ovary. Although several putative isoforms of GnRHR have been identified, it is clear that, in humans, both GnRH-I and GnRH-II signal through a single receptor, GnRHR-I. GnRH-I, GnRH-II, and GnRHR-I mRNA and protein have been identified in placenta and regulate the β-subunit of human chorionic gonadotropin production, which is essential for the maintenance of early pregnancy. They may also play a role in the autocrine/paracrine regulation of trophoblast invasion through extracellular matrix remodeling.


CONCLUSIONS
GnRH-I and GnRH-II have multiple extrapituitary roles. In placenta, they bind to GnRHR-I to stimulate the production of β-subunit of human chorionic gonadotropin. They may also play a role in trophoblast invasion. A better understanding of the molecular mechanisms involved in GnRH/GnRHR signaling at the maternal-fetal interface may identify novel roles for GnRH agonists/antagonists in the prevention or treatment of hormonally mediated diseases.
Department of Obstetrics & Gynecology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Kirsten
K
Sasaki
Errol R
ER
Norwitz
D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011966:Receptors, LHRH / Q000378:metabolism*; D015398:Signal Transduction
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone