The luteinizing hormone receptor

The luteinizing hormone (LH) receptor belongs to a small family of C protein-coupled receptors for pituitary and placental glycoprotein hormones. LH receptors in the testis and ovary activate cyclic AMP-dependent pathways that promote the growth and steroidogenic activity of Leydig cells and ovarian interstitial, granulosa, and luteal cells. The ovarian receptors are also coupled to phosphoinositide and calcium signaling responses. LH receptors are characterized by large extracellular hormone-binding regions fused to seven-transmembrane-domain modules that subserve C protein activation. They depend on specific glycosyl chains for folding and conformational stability of the binding domain. The extracellular region containing the binding domain of the receptor is encoded by 10 exons, and the remainder is encoded by a single exon. In addition to the holoreceptor, splice variants and truncated forms are expressed in the gonads. Several naturally occurring mutations in the transmembrane regions of the LH receptor cause constitutive activation and Leydig cell hyperfunction in patients with familial precocious puberty. Inactivating mutations are present in subjects with Leydig cell hypoplasia. These natural mutations are providing insights into the molecular mechanisms of signal transduction. Definition of the transcriptional regulatory elements in the promoter of the LH receptor is beginning to elucidate the mechanisms of its transcriptional regulation and its tissue-specific and developmental patterns of expression.