3 beta hydroxysteroid dehydrogenase deficiency

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) locally regenerates active glucocorticoids from their inert forms thereby amplifying intracellular levels within target tissues including the brain. We previously showed greater increases in intra-hippocampal corticosterone (CORT) levels upon Y-maze testing in aged wild-type than in 11β-HSD1(-/-) mice coinciding with impaired and intact spatial memory, respectively. Here we examined whether ageing influences 11β-HSD1 regulation of CORT in the dorsal hippocampus under basal conditions during the diurnal cycle and following stress...

Inherited diseases are the result of DNA sequence changes. In recessive diseases, the clinical phenotype results from the combined functional effects of variants in both copies of the gene. In some diseases there is often considerable variability of clinical presentation or disease severity, which may be predicted by the genotype. Additional effects may be triggered by environmental factors, as well as genetic modifiers which could be nucleotide polymorphisms in related genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the phenotype of SLOS individuals...

CONTEXT: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear. HYPOTHESIS: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation. DESIGN AND SETTING: This was a double-blind, placebo-controlled, parallel, 3-month study. PARTICIPANTS AND INTERVENTION: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections...

CONTEXT: Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. OBJECTIVE: This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. DESIGN, SETTING, AND PARTICIPANTS: Fifty-four women who underwent in vitro fertilization were enrolled. INTERVENTION: Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles...

Congenital adrenal hyperplasia (CAH) is an autosomal recessive defect in steroidogenesis, mostly affecting 21-hydroxylase enzyme deficiency. The other seldom cortisol synthesis abnormalities include deficiencies of: 11beta-hydroxylase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxylase, 17,20-lase and 11 beta-hydroxysteroid dwehydrogenase type 1. There are three main types, depending on the clinical level of 21-hydroxylase deficiency: (1) classical form--salt-wasting CAH (2) the classical form non- salt-wasting (3) non-classical form...

BACKGROUND: Prenatal malnutrition can affect the phenotype of offspring by changing epigenetic regulation of specific genes. Several lines of evidence demonstrate that calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. We hypothesized that pregnant female rats fed a Ca-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and that lactation would modify these alterations. METHODOLOGY: We determined the effects of Ca deficiency during pregnancy and/or lactation on hepatic 11β-hydroxysteroid dehydrogenase-1 (Hsd11b1) expression in offspring...

Prenatal undernutrition affects offspring phenotype via changes in the epigenetic regulation of specific genes. We hypothesized that pregnant females that were fed a calcium (Ca)-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and altered epigenetic gene regulation. Female Wistar rats ate either a Ca-deficient or control diet from 3 weeks before conception to 21 days after parturition. Pups were allowed to nurse from their original mothers and then euthanized on day 21...

BACKGROUND: Decidualizing human endometrial stromal cells (HESCs) profoundly up-regulate 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), the enzyme that converts inert cortisone to active cortisol. We postulated that the induction of a cortisol gradient upon decidualization of the periimplantation endometrium may impact on the uterine natural killer (uNK) cell population and on local expression of corticosteroid-dependent target genes. METHODS: Midluteal endometrial biopsies (n = 55) were processed for uNK cell (CD56) analysis and primary HESC cultures...

17-β-Hydroxysteroid dehydrogenase type 3 deficiency is a rare autosomal recessive cause of 46,XY disorder of sex development. Worldwide, about 30 mutations in the hydroxysteroid (17-beta) dehydrogenase 3 (HSD17B3) gene have been reported, involving all exons except exon 1. Herein, we investigated an Egyptian female with 46,XY karyotype and low testosterone/Δ4-androstenedione ratio. Genomic DNA was extracted from blood samples, and then, direct DNA sequencing of HSD17B3 gene was performed. The patient had a homozygous mutation c...

The syndrome of apparent mineralocorticoid excess (AME) is an autosomal recessive disorder characterized by hypertension, hypokalemia, low renin, and hypoaldosteronism. It is caused by deficiency of 11β-hydroxysteroid dehydrogenase, which results in a defect of the peripheral metabolism of cortisol to cortisone. As a consequence, the serum cortisol half-life (T½) is prolonged, ACTH is suppressed, and serum cortisol concentration is normal. The hormonal diagnosis of the disorder is made by the increased ratio of urine-free cortisol to cortisone...

17-beta-Hydroxysteroid dehydrogenase type 3 (17betaHSD-3) converts delta4 androstenedione (A) to testosterone (T) in the testes. This enzyme plays a key role in androgen synthesis and it is essential for normal fetal development of male genitalia. 17betaHSD-3 deficiency is a rare cause of 46,XY disorders of sexual development. Here, we report a 16-year-old 46,XY patient with 17betaHSD-3 deficiency raised as a female and significantly virilized in puberty. A homozygous 7 base pair deletion on exon 10 was determined in HSD17B3 gene (c...

AIM: Hereditary endocrinopathies in Cyprus exhibit evidence of a founder effect and display the influence of past migration patterns. The genetic frequency and mutation pattern of a specific disorder of sex development (DSD), which is classified as 46,XX DSD or 46,XY DSD, and the non-classic form of congenital adrenal hyperplasia (NC-CAH) outline a type of genetic drift. RESULTS: Not only the high prevalence of the NC-CAH p.V281L mutation but also the rarity of CAH large lesions present a genetic diversity similar to that observed in the Middle Eastern countries...

AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in metabolic tissues (muscle and liver) and has been identified as a modulator of the female reproductive functions. However, its function in the testis has not yet been clearly defined. We have investigated the potential role of AMPK in male reproduction by using transgenic mice lacking the activity of AMPK catalytic subunit α1 gene [α1AMPK knockout (KO)]. In the testis, the α1AMPK subunit is expressed in germ cells and also in somatic cells (Sertoli and Leydig cells)...

Mutations of 3 beta hydroxysteroid dehydrogenase type II (HSD3B2) gene result in different clinical consequences. We explain a patient who demonstrated a salt wasting form of 3βHSD deficiency in infancy. Signs of hyponatremia and hyperkalemia were recognized in the infant with ambiguous genitalia and perineal hypospadias. The 46,XY male was genotyped by direct sequencing of HSD3B2 gene. Steroid profiles showed elevated concentration of 17 hydroxyprogesterone, and decrease in concentration of cortisol, and testosterone...

Recent trials show salicylates improve glycemic control in type 2 diabetes, but the mechanism is poorly understood. Expression of the glucocorticoid-generating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue is increased in vitro by proinflammatory cytokines and upregulated in obesity. 11β-HSD1 inhibition enhances insulin sensitivity. We hypothesized that salicylates downregulate 11β-HSD1 expression, contributing to their metabolic efficacy. We treated diet-induced obese (DIO) 11β-HSD1-deficient mice and C57Bl/6 mice with sodium salicylate for 4 weeks...

We investigated the acute stress response in a common carp strain (E5) with interrenal hyperplasia due to 17α-hydroxylase deficiency, and in an isogenic standard (STD) carp strain. Cortisol, corticosterone and the head kidney-somatic index were measured during and after a 3 h net confinement stress. Star, cyp17a2, hsd3b, cyp21, hsd11b2 mRNA levels were measured in head kidneys using real-time qPCR. The results show very high corticosterone levels and enlargement of the head kidney in E5 fish. This is the first report in a teleost fish showing a significant increase of corticosterone levels in response to stress due to interrenal hyperplasia...

Vitamin B(12) (cobalamin) deficiency results in atrophy of seminiferous tubules and aplasia of spermatozoa and spermatid. The transmembrane protein amnionless (AMN) directs endocytosis of cubilin with its ligand, contributing to intrinsic factor-vitamin B(12) absorption. To understand vitamin B(12) transport in testis, we analysed AMN expression in developing mouse testes and in Leydig cells and speculated the possible role of AMN in testis. In testes, Amn mRNA levels were low until 14 days post partum (pp) and markedly increased from puberty onwards...

Hydroxysteroid (17β) dehydrogenase 10 (HSD10), the HSD17B10 gene product, is a mitochondrial NAD(+)-dependent dehydrogenase. There are two outstanding features of this vital enzyme: (a) the versatility of its catalytic endowment is attributed to the flexibility of its active site to accommodate diverse substrates such as steroids, fatty acids, bile acid, and xenobiotics; (b) its capacity to bind other proteins and peptides. For example, it tightly binds with three identical subunits to compose a homotetramer...

Prenatal under-nutrition involves changes in the epigenetic regulation of specific genes. Maternal magnesium (Mg) deficiency affects maternal glucocorticoid metabolism, but the mechanisms underlying changes in glucocorticoid homeostasis of offspring are not well understood. In this study, we investigated the effects of feeding pregnant rats a Mg-deficient diet (0.003% magnesium) on the methylation of cytosine-guanine (CpG) dinucleotides in hepatic glucocorticoid genes of neonatal offspring, compared with controls (0...

Mineralocorticoid receptor (MR) activation is proinflammatory and proatherogenic. Antagonism of MR improves survival in humans with congestive heart failure caused by atherosclerotic disease. In animal models, activation of MR exacerbates atherosclerosis. The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) prevents inappropriate activation of the MR by inactivating glucocorticoids in mineralocorticoid-target tissues. To determine whether glucocorticoid-mediated activation of MR increases atheromatous plaque formation, we generated Apoe(-/-)/11β-HSD2(-/-) double-knockout (E/b2) mice...