Background: Infertility is an important issue for couples that may cause various psychological and emotional problems. Female infertility disorders play a major role in approximately 50-80% of the ...causes of infertility in various areas in Nigeria. Moringa oleifera has been proposed as a plant with female fertility enhancement effects. The objective of this study was to assess the fertility-improving effects of ethanol extract of M. oleifera leaf and to determine the phytochemical components causing these effects by in silico analyses. Methods: The in vitro effects on fertility were evaluated using Drosophila melanogaster (fruit fly) because of its genetic similarities to humans. The copulation duration, mating latency, and the number of emergences from the fruit fly after mating were determined. Three doses (0.025%, 0.05%, and 0.1% w/w) of the M. oleifera ethanol extract were administered to three different groups, while a control group only received feed mixed with ethanol. For in silico studies, 62 compounds were obtained from the PubChem library by mining compounds from articles related to M. oleifera. Next, a ligand library was generated and docked against various targets of interest (estrogen, progesterone, kisspeptin, liver X, PPARG, and 15-PGDH receptors as well as 17β hydroxysteroid dehydrogenase and insulin-degrading enzymes) which have female fertility-enhancing effects. Results: The in vivo experiments showed that M. oleifera had no effect on copulation duration and mating latency, but interestingly, it enhanced the fertility/emergence of the treated fruit flies. In silico studies suggested that phytochemicals such as rutin, marumoside B, myricetin, and quercetin showed docking scores that may well support previous works on M. oleifera enhancement of female fertility. Conclusion: The results showed that M. oleifera can enhance fertility in female fruit flies.
The enzyme 17-β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) catalyzes the biosynthesis of testosterone (T) from Δ4-androstenedione, and plays an important role in the final steps of androgen ...synthesis. 17β-HSD3 deficiency originates from mutations in the HSD17B gene, causing an autosomal recessive 46,XY sex developmental disorder (DSD). Patients with 46,XY karyotype can exhibit a wide phenotypic spectrum, varying from complete external female genitalia to male genitalia with hypospadias. Here we report a case of 17β-HSD3 deficiency diagnosed in the infantile period who was later found to have a novel
gene variation. The 14-month old patient, who exhibited a female phenotype, presented with a bilateral lump in the inguinal area. Imaging revealed bilateral testicular gonads in the inguinal area. Hormonal evaluation showed low levels of basal and stimulated serum T, a high level of androstenedione (A), and a low T/A ratio. Chromosomal analysis showed 46,XY karyotype. Sequence analysis of the
gene revealed a c.673_1G>C homozygous class 2 (splice site) variation in intron 9. The consanguineous parents were sequenced, and both were heterozygous for the same mutation. This variation has not been previously reported in the literature. In conclusion, a 46,XY DSD should be considered in patients with a female phenotype who exhibit gonad(s) in the inguinal area at an early age. Furthermore, in patients with insufficient T synthesis and high levels of androstenedione, 17β-HSD3 should be considered, and molecular analysis should be done for a definitive diagnosis and subsequent genetic counseling.
The concept of metamorphosis (change of form, structure, or substance) is very frequently encountered in Ancient Greek and Roman literature. One of the most striking types of metamorphosis described ...in many myths is gender transformation, where a man becomes a woman or vice versa. Herein, we present a case of pubertal gender inversion, the marvelous story of the Cretan Leucippus, which not only inspired many ancient writers but also led to the development of a distinct, local, religious cult. A medical interpretation of the myth, whereby we attempt to establish a diagnosis for this case of heterosexual puberty, is also provided.
Objectives
Puberphonia or mutational falsetto (MF) is seen more in males, and hormonal changes are considered to be among the aetiological causes. Therefore, the aim of this study was to investigate ...the molecules G protein-coupled oestrogen receptor 1 (GPER-1), aromatase, 17-beta-hydroxysteroid dehydrogenase (17β-HSD), cyclic adenosine monophosphate (cAMP) levels related to receptors and pathways in patients with MF.
Methods
The study included 30 MF patients and a control group of 30 healthy individuals. Voice recordings were made of the MF patients and acoustic analyses were applied. The serum GPER-1, aromatase, 17β-HSD, cAMP levels and TSH, estradiol, prolactin, progesterone, and testosterone levels were evaluated in venous blood samples.
Results
In the MF patients, the GPER-1 level determined of mean 3.68 (1.95–4.26) pg/ml, 17 beta dehydrogenase of 5.25 (2.73–6.77) ng/ml, and cAMP of 24.62 (11.62–30.35) ng/ml were statistically signficantly higher than those of the control group (
p
= 0.008,
p
= 0.002,
p
= 0.003, respectively). The aromatase level in the MF patients was found to be 3.48 (2.01–4.91) and the difference between the two groups was not statistically significant (
p
= 0.067).
Conclusion
The GPER-1, 17β-HSD, and cAMP levels were found to be higher in the MF patients than in the control group, suggesting that they could be of importance in the diagnosis and treatment of MF.
Intratumoral metabolism and synthesis of estrogens as a result of the interactions of various enzymes are considered to play very important roles in the pathogenesis and development of hormone ...dependent breast carcinoma. Among these enzymes, intratumoral aromatase plays as important role converting serum androgens to estrogens in situ, and serves as a source of estrogen, especially in postmenopausal patients with breast carcinoma. However, other enzymes such as the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, estrogen sulfatase (STS) and estrogen sulfotransferase, also play pivotal roles in intratumoral estrogen production. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone (E1), and thereby serve to modulate the tissue levels of bioactive E2 in human breast carcinoma. 17Beta-HSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2), whereas 17beta-HSD type 2 catalyzes primarily the oxidation of E2 to E1. In human breast disease, 17beta-HSD type 1 is expressed in proliferative disease without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17Beta-HSD type 2 has not been detected in any of these breast lesions. In addition, 17beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E1, produced as a result of in situ aromatization, to E2, a biologically potent estrogen, which exerts estrogenic actions on tumor cells through estrogen receptor, especially the alpha subtype in carcinoma cells. Therefore, inhibiting intratumoral 17beta-HSD type 1 is also considered to contribute to inhibition of cell proliferation by decreasing intratumoral estradiol. Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, while steroid sulfatase (STS) hydrolyzes estrone sulfate (E1-S) to estrone. EST immunoreactivity was recently demonstrated to be significantly associated with a decreased risk of recurrence or improved prognosis by both uni- and multivariate analyses. STS immunoreactivity was significantly associated with an increased risk of recurrence by univariate analysis. These findings also suggest that EST and STS plays important roles in regulation of in situ estrogen production, and EST especially is a potent prognostic factor in human breast carcinoma. Therefore, the inhibition of intratumoral STS might also serve as an endocrine therapy in postmenopausal patients. It is also important to note that the status of intratumoral aromatase, 17beta-HSD type 1, EST and STS in human breast cancer tissues is variable and not necessarily correlated with each other, which suggests different potential sources of intratumoral estrogens among individual patients with breast cancer. These findings indicate that there are patients who could benefit more from inhibition of these intratumoral enzymes rather than aromatase inhibition as an endocrine therapy. Therefore, it will become very important to examine the intratumoral levels of 17beta-HSD type 1 and STS in the resected specimens of human breast carcinoma as potential targets of novel endocrine therapy in the near future.
The present article summarizes some of the studies available on steroid hormone conversion through the specific expression of steroidogenic enzymes in adipose tissue (adipose tissue intracrinology) ...and discusses the potential impact of local adipose tissue steroid metabolism on the regulation of adipocyte function and other metabolic parameters. Several studies have demonstrated significant steroid hormone uptake and conversion by adipose tissues from various body sites and in various cell fractions. Activities and/or mRNAs of aromatase, 3beta-hydroxysteroid dehydrogenase (HSD), 3alpha-HSD, 11beta-HSD, 17beta-HSD, 7alpha-hydroxylase, 17alpha-hydroxylase, 5alpha-reductase and UDP-glucuronosyltransferase 2B15 have been detected in adipose tissue or adipose cells. These studies have demonstrated potentially important roles for these enzymes in obesity, central fat accumulation, and the metabolic syndrome. Future studies on adipose tissue intracrinology will contribute further to our understanding of steroid action in adipocytes.
Background
HSD10 mitochondrial disease (HSD10MD), originally described as a deficiency of 2‐methyl‐3‐hydroxybutyryl‐CoA dehydrogenase (MHBD), is a rare X‐linked disorder of a moonlighting protein ...encoded by the HSD17B10. The diagnosis is usually first suspected on finding elevated isoleucine degradation metabolites in urine, reflecting decreased MHBD activity. However, it is now known that clinical disease pathogenesis reflects other independent functions of the HSD10 protein; particularly its essential role in mitochondrial transcript processing and tRNA maturation. The classical phenotype of HSD10MD in affected males is an infantile‐onset progressive neurodegenerative disorder associated with severe mitochondrial dysfunction.
Patients, Methods, and Results
In four unrelated families, we identified index patients with MHBD deficiency, which implied a diagnosis of HSD10MD. Each index patient was independently investigated because of neurological or developmental concerns. All had persistent elevations of urinary 2‐methyl‐3‐hydroxybutyric acid and tiglylglycine. Analysis of HSD17B10 identified a single missense variant, c.364C>G, p.Leu122Val, in each case. This rare variant (1/183336 alleles in gnomAD) was previously reported in one Dutch patient and was described as pathogenic. The geographic origins of our families and results of haplotype analysis together provide evidence of a founder effect for this variant in Quebec. Notably, we identified an asymptomatic hemizygous adult male in one family, while a second independent genetic disorder contributed substantially to the clinical phenotypes observed in probands from two other families.
Conclusion
The phenotype associated with p.Leu122Val in HSD17B10 currently appears to be attenuated and nonprogressive. This report widens the spectrum of phenotypic severity of HSD10MD and contributes to genotype–phenotype correlation. At present, we consider p.Leu122Val a “variant of uncertain significance.” Nonetheless, careful follow‐up of our patients remains advisable, to assess long‐term clinical course and ensure appropriate management. It will also be important to identify other potential patients in our population and to characterize their phenotype.
HSD10 mitochondrial disease (HSD10MD) is a rare X‐linked disorder, with a classical phenotype of infantile‐onset progressive neurodegeneration associated with severe mitochondrial dysfunction. We describe patients from four unrelated families, showing an unusually mild clinical phenotype. All patients have the p.Leu122Val variant in the HSD17B10, reflecting a founder effect.
17-β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is an important enzyme involved in the final steps of androgen synthesis and is required for the development of normal male external genitalia. ...46,XY individuals with deficiency of this enzyme present a wide clinical spectrum from a female appearance of the external genitalia through ambiguous genitalia to a predominantly male genitalia with micropenis or hypospadias. This paper reports a one-year-old 46,XY patient with 17β-HSD3 deficiency who presented with female external genitalia and bilaterally palpable gonads in the inguinal region. The low T/Δ4 ratio after human chorionic gonadotropin (hCG) stimulation suggested 17β-HSD3 deficiency. A homozygous mutation, c.761_762delAG, was determined at the intron 9/exon 10 splice site of the HSD17B3 gene. To the best of our knowledge, this mutation has not been reported thus far, but its localization and type would imply a complete disruption of the 17β-HSD3 which may explain the phenotype of our patient.
Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external ...genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.
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