G Protein-Coupled Receptors as Targets for Prolactin Actions

Prolactin (PRL) is known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, and immunomodulation. The first step in PRL action involves its interaction with a specific membrane receptor that belongs to the cytokine receptor superfamily. In spite of the lack of a kinase domain, receptors of the cytokine superfamily induce tyrosine phosphorylation of cellular substrates including the receptors. The role of PRL in female reproductive functions is well known and a direct effect on ovarian and testicular steroidogenesis has been established. In the ovary, PRL binds to a specific membrane receptor and exerts an inhibitory effect on follicular steroidogenesis. This effect is the result of an impairment involving FSH stimulation of G protein-coupled receptors (GPCR) and cyclic AMP-mediated activation of aromatase cytochrome P450 gene expression. This observation may indicate a direct connection between tyrosine phosphorylation and follicle-stimulating hormone (FSH) receptor (FSHR) transduction pathways, as is the case for growth factor receptors with intrinsic tyrosine kinase activity, which share several downstream signaling elements with GPCRs. Some studies leading to our understanding of these pathways are reviewed.