Pituitary response to luteinizing hormone-releasing hormone in women with variant luteinizing hormone

Abstract

Objective: To assess the LH response of the pituitary gland to GnRH stimulation in healthy women with a mutant b-subunit (Trp8 to Arg8 and Ile15 to Thr15). Design: Clinical study. Patients: We studied 40 healthy non-pregnant Japanese women of known zygosity for the LH b-subunit gene (3 homozygotes for the mutant gene, 17 heterozygotes, and 20 homozygotes for the wild type). All women had normal ovulatory cycles. Measurements: Serum LH status was determined by comparing LH immunoassays results using a monoclonal antibody recognizing only wild-type LH with those from a polyclonal antibody assay recognizing both variant and wild-type LH. The ratio of monoclonal to polyclonal immunoassay results determined the serum LH status. LH secretion in response to a GnRH stimulation test was measured. Results: All women with the wild-type LH showed a normal response of LH to GnRH according to both assays. Over the time course of the response, the ratios in women with wild-type LH showed no remarkable changes. The response curves in women heterozygous for the mutant peaked 15±30 min after GnRH injection; their response patterns included a statistically signi®cant decrease in the rates of response at 15 min after injection. Conclusions: There are the differences in circulatory kinetics between the two LH forms and in regulation of the two types of LHb genes. The maximal response of the variant LH to pituitary stimulation with GnRH appears to be greater than that of wild-type LH.

Altered Kinetics of Pituitary Response to Gonadotropin-Releasing Hormone in Women with Variant Luteinizing Hormone: Correlation with Ovulatory Disorders

“…In the present study, we investigated the pathophysiological mechanism of ovulatory disorders associated with the variant LH, by examining the serial changes in serum concentrations of variant LH and wild-type LH in response to GnRH stimulation in heterozygous women who had variant LH and wild-type LH. Serum LH was measured by two different immunoassays, one that detects wild-type LH only, while the other detects equally both wild-type LH and variant LH [16]. We have previously demonstrated that the peak level of the variant LH to GnRH-pituitary stimulation was higher than that of wild-type LH [16].…”

“…Serum LH was measured by two different immunoassays, one that detects wild-type LH only, while the other detects equally both wild-type LH and variant LH [16]. We have previously demonstrated that the peak level of the variant LH to GnRH-pituitary stimulation was higher than that of wild-type LH [16]. In the present study, the highest level (4-fold increase compared with baseline) of wild-type LH occurred at 30–60 min after GnRH injection and the highest level (5-fold increase compared with baseline) of variant LH occurred at 15 min after injection both in patients with ovulatory disorders and women with normal ovulatory cycles.…”

“…We previously demonstrated that there are differences in circulatory kinetics between wild-type LH and variant LH, and in regulation of the two types of LHβ genes; the peak response of the variant LH to pituitary stimulation with gonadotropin-releasing hormone (GnRH) was higher than that of the wild-type LH [16]. In the present study, we investigated the difference in LH response to GnRH stimulation between patients with ovulatory disorders and women with normal ovulatory cycles heterozygous for variant LHβ-subunit.…”

A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E ε4 allele

“…Two non-synonymous single nucleotide polymorphisms (SNPs) in LHB are collectively referred to as variant LH (vLH) [ 26 ]. In a study of 40 Japanese women, vLH carriers exhibited greater LH secretion in response to GnRH stimulation [ 27 ]. In breast cancer patients, an LQ-insert in exon 1 of LHCGR was associated with a significantly earlier age of onset and worse survival rate [ 27 ].…”

“…In a study of 40 Japanese women, vLH carriers exhibited greater LH secretion in response to GnRH stimulation [ 27 ]. In breast cancer patients, an LQ-insert in exon 1 of LHCGR was associated with a significantly earlier age of onset and worse survival rate [ 27 ]. Exon 10 of LHCGR is required for binding of LH [ 28 ] and is the location of 2 relatively common non-synonymous SNPs [ 29 ].…”