Hormones in male sexual development

Nef, Serge; Parada, Luis F.

doi:10.1101/gad.843800

Cited by 174 publications

(111 citation statements)

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“…T is essential for the development of the male reproductive system and the maintenance of male reproductive functions (1,2). In addition to defects in reproductive system, its deficiency in the adult contributes to other symptoms that include increased body fat, decreased muscle mass, increased fatigue, depressed mood, decreased cognitive function (3,4), and reduced immune response (5,6).…”

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confidence: 99%

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

Wang

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

197

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Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.

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confidence: 99%

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

Wang

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

197

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“…Androgens and estrogen are steroid hormones that play critical roles in sexually dimorphic genital development (18). Masculinization of male external genitalia is determined mainly by Significance Birth defects of external genitalia occur at a striking frequency, affecting ∼1:250 live births.…”

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confidence: 99%

Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies

Zheng

Armfield

Cohn

2015

Proc. Natl. Acad. Sci. U.S.A.

105

129

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Congenital penile anomalies (CPAs) are among the most common human birth defects. Reports of CPAs, which include hypospadias, chordee, micropenis, and ambiguous genitalia, have risen sharply in recent decades, but the causes of these malformations are rarely identified. Both genetic anomalies and environmental factors, such as antiandrogenic and estrogenic endocrine disrupting chemicals (EDCs), are suspected to cause CPAs; however, little is known about the temporal window(s) of sensitivity to EDCs, or the tissue-specific roles and downstream targets of the androgen receptor (AR) in external genitalia. Here, we show that the full spectrum of CPAs can be produced by disrupting AR at different developmental stages and in specific cell types in the mouse genital tubercle. Inactivation of AR during a narrow window of prenatal development results in hypospadias and chordee, whereas earlier disruptions cause ambiguous genitalia and later disruptions cause micropenis. The neonatal phase of penile development is controlled by the balance of AR to estrogen receptor α (ERα) activity; either inhibition of androgen or augmentation of estrogen signaling can induce micropenis. AR and ERα have opposite effects on cell division, apoptosis, and regulation of Hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling in the genital tubercle. We identify Indian hedgehog (Ihh) as a novel downstream target of AR in external genitalia and show that conditional deletion of Ihh inhibits penile masculinization. These studies reveal previously unidentified cellular and molecular mechanisms by which antiandrogenic and estrogenic signals induce penile malformations and demonstrate that the timing of endocrine disruption can determine the type of CPA.sexual differentiation | external genitalia | congenital malformation | androgen | hypospadias

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“…Chez notre patiente, I'absence de derives Mulleriens temoigne d'une secretion d'hormone antiMQllerienne (AMH) par les cellules de Sertoli et fait eliminer le diagnostic de dysgenesie gonadique. Sous I'effet de I'AMH, la regression des derives Mulleriens se fait dans le sens cranio-caudal [8,10,12] et se deroule vers la 8eme semaine de gestation, periode oQ I'activite de cette hormone est maximale. Le diagnostic de dysgenesie gonadique etant elimine chez cette patiente, nous devons discuter dans cette observation toutes les causes de pseudohermaphrodisme masculin avec absence de derives Mulleriens.…”

Section: Observationunclassified