SF1 in the Development of the Adrenal Gland and Gonads

Özışık, Gökhan; Achermann, John C.; Meeks, Joshua J.; Jameson, J. Larry

doi:10.1159/000067831

Cited by 58 publications

(33 citation statements)

References 45 publications

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“…Results of recent studies suggest that DAX1 was also detected in the cytoplasm, functioning as a potent corepressor for steroid formone receptors in mammalian cells [30][31][32]. However, in our present study, DAX1 immunoreactivity was clearly detectable in the nuclei of prostate carcinoma cells but not so in their cytoplasm, which is compatible with results of most previously reported studies [19,[21][22][23][24][25][26][27][28]. Therefore, these results all suggest that DAX1 protein is predominantly present in the nuclei of prostate carcinoma cells and may play an important role as a nuclear orphan receptor in human prostate cancer tissues.…”

Section: Discussionsupporting

confidence: 92%

“…DAX1 was previously reported in human testis, ovarian follicle, corpus luteum, and adrenal, and has been in general postulated to be associated with development and steroidogenesis of these tissues [21][22][23][24][25]. The presence of DAX1 was also reported in adrenal, endometrial, and ovarian tumor [19,[26][27][28].…”

Section: Discussionmentioning

confidence: 82%

“…Therefore, DAX1 may play an important role in development of human prostate cancer but not in normal prostate. DAX1 protein has been reported to be localized mainly in the nuclei of various cells and to be postulated to work as a nuclear orphan receptor in the human normal and neoplastic tissues [19,[21][22][23][24][25][26][27][28]. Results of recent studies suggest that DAX1 was also detected in the cytoplasm, functioning as a potent corepressor for steroid formone receptors in mammalian cells [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

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Nuclear Receptor DAX1 in Human Prostate Cancer: A Novel Independent Biological Modulator

et al. 2009

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Abstract. The orphan nuclear receptor DAX1 (dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1; NR0B1) has been known for its various roles in human development, specifically sex determination and steroidogenesis. Its expression has been reported in endocrine and sex steroid-dependent neoplasms such as human adrenocortical, pituitary, endometrial, and ovarian tumors. Prostate cancer is also sex steroid-dependent tumor in which androgens play important roles in the pathogenesis and development via androgen receptor (AR). DAX1 is also reported to repress AR activity in human prostate cancer cell line (LNCaP) but its biological roles have remained unclear in the human prostate cancer. The aim of this study is to examine the expression of DAX1 in human prostate cancer using immunohistochemistry in order to evaluate its possible biological and/or clinical significance. In this study, we examined the DAX1 immunoreactivity in human prostate cancer obtained from surgery (n = 40), and correlated the findings with clinicopathological features of the patients. Twenty-one cases were defined as positive cases for DAX1 immunoreactivity (53%). Immunoreactivity for DAX1 was inversely and significantly correlated with Gleason score (P<0.05). However, DAX1 immunoreactivity was not significantly correlated with the status of sex steroid receptors we examined. DAX1 immunoreactivity is considered a new biological modulator of human prostate cancer, but independent to the status of sex steroid receptors in human prostate cancer tissues.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Nuclear Receptor DAX1 in Human Prostate Cancer: A Novel Independent Biological Modulator

et al. 2009

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“…In addition, in both males and females, SF-1 is a key promoter of gonadal hormone production, by regulating the transcription of several genes involved in steroidogenesis (1)(2)(3). SF-1 mainly acts through direct binding to the promoter regions of its target genes, however, indirect effects have also been studied (1,2,4).…”

Section: Introductionmentioning

confidence: 99%

Pubertal androgenization and gonadal histology in two 46,XY adolescents with NR5A1 mutations and predominantly female phenotype at birth

Cools

Hoebeke

Wolffenbuttel

et al. 2012

European Journal of Endocrinology

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Objective: Most patients with NR5A1 (SF-1) mutations and poor virilization at birth are sex-assigned female and receive early gonadectomy. Although studies in pituitary-specific Sf-1 knockout mice suggest hypogonadotropic hypogonadism, little is known about endocrine function at puberty and on germ cell tumor risk in patients with SF-1 mutations. This study reports on the natural course during puberty and on gonadal histology in two adolescents with SF-1 mutations and predominantly female phenotype at birth. Design and methods: Clinical and hormonal data and histopathological studies are reported in one male and one female adolescent with, respectively, a nonsense mutation (c.9TOA, p.Tyr3X) and a deletion of the first two coding exons (NCBI36/hg18 Chr9:g.(126306276-126307705)_(126303229-126302828)del) of NR5A1, both predicted to fully disrupt gene function. Results: LH and testosterone concentrations were in the normal male range, virilization was disproportionate to the neonatal phenotype. In the girl, gonadectomy at 13 years revealed incomplete spermatogenesis and bilateral precursor lesions of testicular carcinoma in situ. In the boy, at the age of 12, numerous germ cells without signs of malignancy were present in bilateral testicular biopsy specimen. Conclusions: In SF-1 mutations, the neonatal phenotype poorly predicts virilization at puberty. Even in poorly virilized cases at birth, male gender assignment may allow spontaneous puberty without signs of hypogonadotropic hypogonadism, and possibly fertility. Patients with SF-1 mutations are at increased risk for malignant germ cell tumors. In case of preserved gonads, early orchidopexy and germ cell tumor screening is warranted. The finding of premalignant and/or malignant changes should prompt gonadectomy or possibly irradiation.

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“…However, recent studies suggest that the major factors regulating adrenal functions in the first weeks are the transcription factors steroidogenic factor 1 and the nuclear hormone receptor DAX1 (26,27). Growth factors such as IGF-1 and IGF-2 are also important for the growth of the gland (28).…”

Section: Hormonal Control Of Adrenal Developmentmentioning

confidence: 99%

A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland

Chamoux

Otis²,

Gallo‐Payet³

2005

Braz J Med Biol Res

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The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies.

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SF1 in the Development of the Adrenal Gland and Gonads

Cited by 58 publications

References 45 publications

Nuclear Receptor DAX1 in Human Prostate Cancer: A Novel Independent Biological Modulator

Nuclear Receptor DAX1 in Human Prostate Cancer: A Novel Independent Biological Modulator

Pubertal androgenization and gonadal histology in two 46,XY adolescents with NR5A1 mutations and predominantly female phenotype at birth

A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland

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