(8, 9). Unlike the cysteine-rich sterol/steroid-binding proteins in serum vitamin D-binding protein/albumin (9) and vitamin D/steroid receptor protein (10) families, which are confined prinicipally to the extracellular domain and nucleus, respectively, IDBP is a relatively abundant, cysteine-poor protein concentrated in, but not confined to, the cytoplasmic compartment of cells (11). However, like these other sterol/steroidbinding proteins (8,9), IDBP has been shown preferentially to bind 25-hydroxylated vitamin D metabolites (12). In the current report we have greatly expanded the vitamin D metabolite-IDBP binding studies to define more clearly which structural modifications of the vitamin D molecule are important for either enhancing or reducing ligand binding to IDBP extracted from NWP cells. We also document the IDBP binding potential of a much more extensive panel of molecules in an attempt to define additional classes of small, lipid-soluble signaling molecules which may interact with IDBP. Although we were previously able to enrich vitamin D metabolite binding activity in extracts of NWP cells (13), attempts to purify IDBP to homogeneity were unsuccessful. Here we report the purification and structural identification of the NWP IDBP as a member of the hsp-70 family of proteins and demonstrate the sterol/steroid binding properties of hsp-70-like proteins. D Sterols, Steroids, 3 H]Hydroxyvitamin D 3 (25-[ 3 H]OHD 3 ; specific activity, 181 Ci/mmol) and MATERIALS AND METHODS Vitamin
Urine sampling via a centralized national laboratory was efficient and cost-saving. Iodine deficiency in Israeli SAC and PW is a serious public-health concern. A national program of salt iodization and iodine supplementation of PW should be urgently considered.
ORMAL pubertal development and fertility depend on the intricate interplay of hypothalamic, pituitary, and gonadal factors. Crucial in this respect are normal secretory patterns of follicle-stimulating hormone and luteinizing hormone. These hormones stimulate the production of estrogen and ovulation in women and the production of testosterone and spermatogenesis in men. Secreted from common gonadotroph cells, the hormones are heterodimers composed of a common a -subunit and a specific b -subunit, each encoded by a separate gene. Specificity of action depends on the recognition of these hormones by specific receptors on the surface of gonadal cells.Various genetic defects of the hypothalamic-pituitary-gonadal axis that cause hypogonadism have been identified. 1 At the level of the hypothalamus, secretion of gonadotropin-releasing hormone is disturbed by mutations in the KAL gene, 2 leading to Kallmann's syndrome, and in the DAX-1 gene, 3 causing X-linked adrenal hypoplasia and hypogonadotropic hypogonadism. At the pituitary level, mutations in the gene for the b -subunit of luteinizing hormone 4 cause hypogonadotropic hypogonadism, and at the gonadal level, loss-of-function mutations in the genes that encode the receptors for folliclestimulating hormone and luteinizing hormone cause hypergonadotropic hypogonadism. 5,6 Specifically, mutations in the gene for luteinizing hormone receptors result in Leydig-cell hypoplasia and undermasculinization in genetic males, 5,7,8 whereas mutations in the gene for follicle-stimulating hormone receptors cause primary gonadal failure and hypergonadotropic hypogonadism in genetic females. 6 Two female patients with follicle-stimulating hor-N mone deficiency caused by mutations in the gene for the b -subunit of follicle-stimulating hormone have been described. One presented with primary amenorrhea and infertility, 9 and the other with delayed puberty. 10 In this report, we describe a man with impaired secretion of follicle-stimulating hormone caused by a homozygous mutation in the gene for the b -subunit of follicle-stimulating hormone, as well as two asymptomatic heterozygous male members of his family. METHODS SubjectsThe proband was referred to our center at the age of 18 years for evaluation of delayed puberty. He reported normal erections and ejaculatory orgasms. He had a prepubertal physique and underdeveloped muscles. He was 178 cm tall (69th percentile) and weighed 59 kg. He had pubic hair (Tanner stage 4), scant axillary hair, and no facial hair. No breast tissue was palpated. The scrotum was thin, and two small, soft testicles (testicular volume, 1 to 2 ml) were palpated. There was no family history of consanguinity, infertility, or delayed puberty.Laboratory studies revealed low serum testosterone and follicle-stimulating hormone concentrations and high serum luteinizing hormone concentrations (Table 1). Serum thyrotropin, prolactin, and cortisol concentrations were normal. Chromosomal analysis revealed a 46,XY karyotype. After intravenous administration of 100 µg of gon...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.