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Sex Chromosome Anomalies
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
L. Hamerton John, A. Evans Jane
SRY is a transcription factor whose function is to initiate testicular differentiation in mammalian embryogenesis. The protein contains a high mobility group box (HMG), a DNA binding motif conserved among a broad class of nuclear proteins. Almost all of the published mutations associated with sex reversal in 46,XY females are located in the HMG box and affect the structure of the DNA binding domain (146). Other loci involved in XY sex reversal include SOX9 at 17q24, a transcription factor whose duplication leads to XX sex reversal, while mutations lead to XY gonadal dysgenesis and campomelic dysplasia. Mutations in SF1 at 9q33 result in adrenal insufficiency and XY gonadal dysgenesis. Mutations in DMRT1 at 9p24 result in XY gonadal dysgenesis. Mutations at the DAX1 locus, an antitestis gene at Xp21.3, result in congenital adrenal hypoplasia, while duplications of a 160 kb region result in XY gonadal dysgenesis (158). Clearly, extensive genetic heterogeneity exists in both XX and XY sex reversal. The process of sex determination is clearly highly complex and only partially understood (153,158-160).
Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Corticotropin (ACTH) and cAMP can regulate CYP11A1. ACTH is a hormone that is released from the anterior pituitary in response to stress. In bovine, the two Sp1-binding sites in the CYP11A1 gene control cAMP transcription though the protein kinase A signaling pathway. The steroidogenic factor 1 (SF1) activates CYP11A1 transcription through interaction with protein factors upstream (Chung et al. 1997). An upstream CREB region and an AP-1 site are involved in cAMP response. The TATA box drives cell type–specific cAMP transcription. SF1 also interacts with Sp1. The expression of CYP11A1 is inhibited by the nuclear receptor DAX-1. All these factors are involved in the regulation of the CYP11A1 gene.
Cushing’s syndrome, cortical carcinoma, and estrogen- and androgen-secreting tumors
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Immunohistochemistry is becoming increasingly useful in determining the diagnosis and prognosis of ACC. Steroidogenic factor-1 (SF-1) has become the marker of choice for determining adrenal origin of a tumor with high sensitivity and specificity. Furthermore, it has been shown to be a stage-independent predictor of prognosis [190, 191]. Quantification of proliferation marker Ki67 has recently been demonstrated as a significant prognostic indicator. In two large ENSAT trials, Ki67 was strongly predictive of both recurrence risk after R0 resection and risk of death in patients with unresectable disease.
Female infertility caused by organophosphates: an insight into the latest biochemical and histomorphological findings
Published in Toxin Reviews, 2023
Mohammad Samare-Najaf, Ali Samareh, Bahia Namavar Jahromi, Navid Jamali, Sina Vakili, Majid Mohsenizadeh, Cain C. T. Clark, Ali Abbasi, Nastaran Khajehyar
OPs-induced alterations in the expression of steroidogenic factor-1, a main regulator of steroid hormone biosynthesis, could disrupt the production of ovarian hormones (Armiliato et al.2014). Since the production of estradiol from testosterone requires the appropriate performance of aromatase, increasing ovarian testosterone levels and decreasing estradiol after exposure to OPs indicates the suppressive impact on the enzyme activity (Brandt et al.2015). Concerning the pivotal impact of ovarian hormones on the maturation of the oocytes, which is an irreplaceable step in the production of fertilizable eggs, acephate could interfere with the nongenomic action of progesterone on the meiotic maturation of oocytes, which is the activation of membrane-receptor associated second messengers, like cAMP or G proteins, through elevating the rate of germinal vesicle breakdown demonstrating the antiestrogenic role of OPs (Das and Thomas 1999, Tokumoto et al.2005, Ghodageri and Katti 2013). In addition to observing similar changes in the gestational embryonic ovary, a ban on sex steroids may be considered one of the main reasons (Ramana et al.1992). Unfortunately, long-term exposure to OPs causes mortality in addition to damaging ovarian tissue (Sumon et al.2019).
Molecular study and genotype–phenotype in Chinese female patients with 46, XY disorders of sex development
Published in Gynecological Endocrinology, 2021
Junke Xia, Jing Wu, Chen Chen, Zhenhua Zhao, Yanchuan Xie, Zhouxian Bai, Xiangdong Kong
The NR5A1 gene (OMIM #184757) encoding steroidogenic factor-1 (SF-1) positively regulates the expression of genes involved in male sex differentiation and modulates the expression of many factors involved in steroid hormone synthesis [25,26]. NR5A1 mutations may cause a defect in androgen biosynthesis and lead to a variable clinical phenotype of male pseudo-hermaphroditism [25]. The phenotype may range from clitoridauxe, virilization, and hypospadias to almost normal testicular function [27]. In our study, NR5A1 mutations were found in patients who presented with cryptorchidism and micropenis. The frame shift mutation p.Pro133Leufs was identified in the hinge region, which is critical for the transcriptional capacity of SF-1 [25]. The frame-shift variant forms a truncated protein with impaired protein function or is degraded by nonsense-mediated mRNA decay.
β-arrestin 2 quenches TLR signaling to facilitate the immune evasion of EPEC
Published in Gut Microbes, 2020
Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Yu Wang, Shichao Huang, Ningning Liu, Chunmei Xia, Nissan Yissachar, Feng Huang, Yiwei Chu, Dapeng Yan
The immune system is exquisitely balanced. Posttranslational modifications (PTMs) such as ubiquitination and phosphorylation play important roles to ensure the delicate balance underlying immune signal transduction. Ubiquitination and phosphorylation are tightly linked and could regulate each other in many cases. For example, K63-linked polyubiquitination of Connexin 43 is induced by its phosphorylation.35 Steroidogenic factor 1 (SF-1) controls sexual development in the embryo, ubiquitination of SF-1 requires its phosphorylation at Ser203.36 E3 ubiquitin ligase binds with phosphorylated β-catenin to mediate its ubiquitination, while mutation of a single serine prevents the ubiquitination.37 These studies show that phosphorylation could regulate ubiquitination. In our study, we found that SHP-1 inhibits K63-linked ubiquitination of TRAF6 and TAK1 by dephosphorylating their certain tyrosine residues, which provide a proof that phosphorylation regulates ubiquitination during the infection.