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Environmental toxicants on Leydig cell function
Published in C. Yan Cheng, Spermatogenesis, 2018
Leping Ye, Xiaoheng Li, Xiaomin Chen, Qingquan Lian, Ren-Shan Ge
No clear mutation of human SRD5A1 has been found to be associated with human diseases. The human SRD5A2 mutation is associated with male pseudohermaphroditism.46 Human SRD5A3 encodes a protein that not only catalyzes testosterone into dihydrotestosterone but also converts polyprenol to dolichol.41 The human SRD5A3 mutation causes a congenital glycosylation disorder but does not affect reproduction.44
The vagina as source and target of androgens: implications for treatment of GSM/VVA, including DHEA
Published in Climacteric, 2023
S. Cipriani, E. Maseroli, S. A. Ravelli, L. Vignozzi
In human distal vaginal tissue samples, the enzymes involved in the reactions upstream of steroidogenesis (steroidogenic acute regulatory protein [STAR], cytochrome P450 11A1 [CYP11A1], CYP17A1) were found to be expressed at much lower levels than in the ovarian tissue [19]. Conversely, the expression of pro-androgenic steroidogenic enzymes such as 17β-hydroxysteroid dehydrogenase type 3 (HSD17β3), 17β-hydroxysteroid dehydrogenase type 5 (HSD17β5) and the three isoforms of 5α-reductase (SRD5A1, SRD5A2 and SRD5A3), implicated in the transformation of testosterone into its most active metabolite, DHT, showed a markedly higher level of expression in the distal vagina than in the ovary [19]. Moreover, mass spectrometry studies revealed a significant increase in androstenedione, testosterone and DHT in the culture medium of hvSMCs, after treatment with increasing concentrations of DHEA, therefore leading to the innovative concept that vaginal muscle cells express the enzymatic machinery necessary to produce the most active metabolites of androgens [19].
24 hour patterning in gene expression of pineal neurosteroid biosynthesis in young chickens (Gallus gallus domesticus L.)
Published in Chronobiology International, 2021
Magdalena Chustecka, Natalia Blügental, Pawel Marek Majewski, Iwona Adamska
Neurosteroid biosynthesis is strongly conserved in all vertebrates, following similar pathways to those in the steroidogenic organs (Tsutsui 2019). Biosynthesis begins with translocation of cholesterol across the mitochondrial membrane by a complex transport mechanism involving several proteins. These include the steroidogenic acute regulatory protein (STAR, synonym STARD1), the translocator protein (TSPO, synonyms PBR, MBR), the adenine nucleotide transporter protein (ANT), and voltage-dependent anion channel protein (VDAC) (Morohaku et al. 2014; Papadopoulos et al. 2018; Selvaraj and Stocco 2015). Pregnenolone (PREG) is then formed by cleavage of the cholesterol side-chain by cytochrome P450scc (E.C 1.14.15.6) encoded by Cyp11a1. PREG is further metabolized in two ways. The first is by hydroxylation to 7α-OH PREG or 7β-hydroxypregnenolone (7β-OH PREG) catalyzed by cytochrome P4507α (E.C 1.14.14.29) encoded by Cyp7b1 (Spg5a). The second is dehydrogenation and isomerization to progesterone (PRO) by 3β-hydroxysteroid dehydrogenase (3β-HSD, E.C 1.1.1.145) encoded by Hsd3b2 (Sdr11e2). PRO can be reduced in two-steps catalyzed by 5α-reductase (E.C 1.3.99.5) encoded by Srd5a1 and 3α-hydroxysteroid dehydrogenase (3α-HSD, E.C 1.3.99.6) encoded by Akr1d1 (Srd5b1) to ALLO. PRO can also be converted to epipregnanolone (EPI) in two steps catalyzed by 3β-HSD and 5β-reductase (E.C 1.3.1.94) encoded by Srd5a3 (Srd5a2l) gene (Figure 1) (Do Rego et al. 2009).
Early-onset retinal dystrophy and chronic dermatitis in a girl with an undiagnosed congenital disorder of glycosylation (SRD5A3-CDG)
Published in Ophthalmic Genetics, 2018
Congenital disorders of glycosylation (CDG syndromes) are a family of multisystem disorders due to abnormal protein and lipid glycosylation (1). Over 100 types have been described to date from variants in different genes. Clinical features and severity vary and can include ocular involvement, but the most recurrent finding is neurological impairment. Biallelic variants in the gene steroid 5α-reductase type 3 (SRD5A3), responsible for the conversion of polyprenol to dolichol, cause SRD5A3-CDG, formally known as Type Iq (2,3). Variants in the gene result in impaired protein N-glycosylation, C-mannosylation, mannose-linked glycan synthesis, and glycophospholipid anchor synthesis. SRD5A3-CDG was first described in two unrelated Baluchi families with iris and chorioretinal colobomas, optic atrophy, atopic dermatitis, cerebellar hypoplasia, and developmental disability (2). Both families harbored the same homozygous SRD5A3 deletion (p.Gln96delinsX) (3). The purpose of this report is to highlight the presentation of a Baluchi girl with early-onset retinal dystrophy, chronic dermatitis, and developmental disability who was found to have undiagnosed SRD5A3-CDG. She was homozygous for the SRD5A3 deletion p.Gln96delinsX but did not have ocular coloboma, which demonstrates that ocular coloboma is not an essential finding in children homozygous for this specific deletion.