A new LH receptor splice mutation responsible for male hypogonadism with subnormal sperm production in the propositus, and infertility with regular cycles in an affected sister

Abstract

LHR mutations may represent an underestimated cause of infertility in women, in addition to being responsible for male hypogonadism with reduced spermatogenesis.

Differential expression of luteinizing hormone receptor, androgen receptor and heat-shock protein 70 in the testis of long-distance transported mice

“…Hormones exert their biological effects through binding with their receptors. The male carriers of homozygous mutation of the LHR gene display delayed puberty, micropenis, and oligospermia, so LHR mutations may be responsible for male hypogonadism with reduced spermatogenesis (Bruysters et al, 2008). Gonadotropins and androgen receptors (AR) play a role in gonadal development (Omran Nel, 2012), and FSH and testosterone are the main hormonal regulators of spermatogenesis (Sofikitis et al, 2008).…”

Alternative splicing of G protein-coupled receptors: physiology and pathophysiology

“…Mutations that lead to loss-offunction in the male are linked with severe phenotypes, such as female external genitalia, micropenis and oligospermia; while in women primary and secondary sexual characteristics develop normally, but infertility is common [131,132]. Bruysters and colleagues have recently described a family that carries a homozygous mutation G→A at position -1 at the intron 10/exon 11 boundary of the LHR gene, resulting in alternative splicing of LHR and an F o r R e v i e w O n l y eight amino acid deletion [53]. In vitro studies have shown that receptor expression is not affected, but the potency of LH (but not human chorionic gonadotropin) is reduced; thus, this LHR isoform shows impaired hormone responsiveness [53].…”

“…Bruysters and colleagues have recently described a family that carries a homozygous mutation G→A at position -1 at the intron 10/exon 11 boundary of the LHR gene, resulting in alternative splicing of LHR and an F o r R e v i e w O n l y eight amino acid deletion [53]. In vitro studies have shown that receptor expression is not affected, but the potency of LH (but not human chorionic gonadotropin) is reduced; thus, this LHR isoform shows impaired hormone responsiveness [53]. A male patient and his three sisters showed reproductive impairment.…”

“…A male patient and his three sisters showed reproductive impairment. The male patient had delayed puberty, micropenis and oligospermia; while two of his sisters were infertile and the third sister had three spontaneous miscarriages [53]. Another splice variant of LHR that results in a frame-shift in the reading frame and creates a truncated receptor composed of the N-terminal ectodomain (responsible for high-affinity ligand binding), causes an alteration in pituitary-gonadal function, and morphological changes in the adrenals and kidneys of transgenic mice [54].…”

The Use of rLH, HMG and hCG in Controlled Ovarian Stimulation for Assisted Reproductive Technologies

“…The specific importance of LH activity can be demonstrated in patients with LHβ or LH receptor gene mutations. Case reports of these male and female patients have demonstrated hypogonadism, infertility, pseudohermaphroditism, and amenorrhea (11)(12)(13). In assisted reproduction technologies (ART), the importance of LH is demonstrated clearly in hypogonadotropic hypogonadic patients.…”