Endocrine Abstracts

Introduction: Kisspeptin is the endogenous ligand for the G-protein coupled receptor-54 (GPR54 or KiSS1R). During human pregnancy, maternal levels of placental kisspeptin dramatically increase 7000-fold. The physiological significance of this is unknown. A potential target could be the fetal adrenal cortex (FAC), which undergoes rapid growth from 10 weeks gestation, predominantly of the inner fetal zone (FZ). The FZ expresses the steroidogenic enzymes needed for conversion of DHEA to its sulphate. Placental estrogen synthesis is dependent on the aromatization of C19 steroid precursors, primarily DHEAS supplied from the FZ. Fetal adrenal steroidogenesis is therefore essential for the function of the feto-placental unit, postulated to play an integral role in the maintenance of pregnancy.

Methods: Immunofluorescence studies were used to characterise the spatio-temporal expression of Kiss1R protein in the human FAC at a range of gestational ages. qRT-PCR was used to investigate Kiss1R mRNA expression in H295R adrenocortical cells as a model of the human FAC. Enzyme immunoassay was used to examine the functional effects of kisspeptin stimulation on steroidogenesis in H295R cells.

Results: Confocal studies demonstrated Kiss1R protein is highly expressed throughout the human FAC, predominantly within the inner FZ, from as early as 10 weeks gestation. RT-PCR studies revealed Kiss1R mRNA is expressed in H295R cells and is significantly decreased following treatment with kisspeptin for 24 h (P<0.001). Enzyme immunoassay demonstrated that kisspeptin stimulation increases DHEAS production by threefold compared to untreated H295R cells (P<0.01).

Conclusions: High levels of kisspeptin may stimulate DHEAS production by the FAC. As pregnancy progresses, down-regulation of Kiss1R may occur to fine-tune steroidogenesis from the FAC. Kisspeptin may be a novel factor with critical regulatory roles in human FAC development and function, and in the maintenance of pregnancy. This reveals a novel insight into the endocrine regulation of the feto-placental unit.