Physiological Androgen Insensitivity of the Fetal, Neonatal, and Early Infantile Testis Is Explained by the Ontogeny of the Androgen Receptor Expression in Sertoli Cells

Chemes, H; Rey, Rodolfo; Nistal, Manuel; Regadera, Javier; Musse, Mariana P.; González‐Peramato, Pilar; Serrano, Álvaro

doi:10.1210/jc.2008-0915

Cited by 173 publications

(113 citation statements)

References 19 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Combined with the observations that Sertoli cells do not express ARs during fetal development in the rodent or human (Shapiro et al 2005, Chemes et al 2008, these data indicate that the effects of androgens must be mediated through another testicular cell type in the fetus. Immunohistochemical data suggest that it is mostly PMC (and some interstitial cells) that express the AR in the testis during fetal development (Majdic et al 1995, Shapiro et al 2005, Chemes et al 2008; Fig. 1), and it appears likely that androgen action on the Sertoli cells is mediated through the PMC.…”

Section: Sertoli Cellsmentioning

confidence: 60%

“…PMC express the AR in the adult animal, and recent studies have begun to show how important androgen actions, via the PMC, are for normal adult testicular function (Welsh et al 2009). In the fetus, the PMC are the main cell type expressing the AR (Majdic et al 1995, Shapiro et al 2005, Chemes et al 2008, and Sertoli cell number is reduced in ARKO and Tfm mice (Johnston et al 2004, Tan et al 2005, suggesting a role for the PMC in fetal Sertoli cell development. In PMC-ARKO mice (lacking AR on the PMC only), the testes appear largely normal at post-natal day 12, suggesting that fetal Sertoli cell development is largely unaffected (Welsh et al 2009).…”

Section: Peritubular Myoid Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Endocrinology of the mammalian fetal testis

O’Shaughnessy¹,

Fowler²

2011

Reproduction

View full text Add to dashboard Cite

The testes are essential endocrine regulators of fetal masculinization and male development and are, themselves, subject to hormonal regulation during gestation. This review focuses, primarily, on this latter control of testicular function. Data available suggest that, in most mammalian species, the testis goes through a period of independent function before the fetal hypothalamic-pituitary-gonadal axis develops at around 50% of gestation. This pituitary-independent phase coincides with the most critical period of fetal masculinization. Thereafter, the fetal testes appear to become pituitary hormone-dependent, concurrent with declining Leydig cell function, but increasing Sertoli cell numbers. The two orders of mammals most commonly used for these types of studies (rodents and primates) appear to represent special cases within this general hypothesis. In terms of testicular function, rodents are born 'early' before the pituitary-dependent phase of fetal development, while the primate testis is dependent upon placental gonadotropin released during the pituitary-independent phase of development.

show abstract

Section: Sertoli Cellsmentioning

confidence: 60%

Section: Peritubular Myoid Cellsmentioning

confidence: 99%

Endocrinology of the mammalian fetal testis

O’Shaughnessy¹,

Fowler²

2011

Reproduction

View full text Add to dashboard Cite

show abstract

“…On the other hand, Van Roijen et al (1995) found no evidence supporting the stagedependent immunoexpression of AR in human testes, and none of the publications that have investigated the localization of testicular AR identified specific variations in AR immunoexpression in the six stages of the human spermatogenic cycle (Takeda et al, 1989;Ruizeveld de Winter et al, 1991;Kimura et al, 1993;Iwamura et al, 1994). SCAR immunostaining is also dependent on the primary antibody concentration, which causes different rates of positive staining of Sertoli cells (Suarez-Quian et al, 1999;Chemes et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Expression of testicular androgen receptor in non‐obstructive azoospermia and its change after hormonal therapy

2014

View full text Add to dashboard Cite

SUMMARYSeveral trials aimed at improving the sperm retrieval from men with non-obstructive azoospermia (NOA) by optimizing intratesticular testosterone (ITT) have reported partial responses, however, an appropriate level of ITT has not been identified. In this study, we examined the expression of the testicular androgen receptor (AR) in NOA and investigated its correlation with clinical and pathological parameters. Expression of the testicular AR was investigated in 52 men with NOA and 22 men with obstructive azoospermia (OA). Twenty-two patients for whom sperm retrieval failed during microdissection testicular sperm extraction (micro-TESE) were enrolled in hormonal therapy using hCG with or without recombinant human follicle stimulating hormone (rhFSH) prior to a second micro-TESE. Sertoli cells were identified by vimentin immunostaining, and positivity in Sertoli cells was used as the AR index. AR immunostaining was robust in the nuclei of Sertoli cells [Sertoli cell androgen receptor (SCAR)] in both OA and NOA. The mean AR index in NOA was significantly higher than that in OA (p < 0.05). In NOA patients, there was no correlation between the AR index and the clinical parameters, whereas the AR index of early maturation arrest (MA) was significantly lower than that of Sertoli cell only, late MA and hypospermatogenesis (p < 0.05). A significant increase in the AR index after salvage hormonal therapy was shown, particularly when using rhFSH. The AR index in patients from whom spermatozoa could be retrieved at the second micro-TESE increased significantly after hormonal therapy. In human testes, the expression of AR is dominant in Sertoli cells, and the expression of SCAR is upregulated by FSH. Germ cell maturation, especially during spermatogonia to spermatocyte stage, has been shown to be SCAR-dependent. Taken together, the results indicate that SCAR elevation is closely associated with sperm retrieval after hormonal therapy and that FSH-based hormonal therapy is potentially effective in NOA men with MA.

show abstract

“…Although clinically unperceivable by palpation, testis size increases in early infancy (Goede et al, 2011) mainly due to the proliferation of Sertoli cells (Nistal et al, 1982;Mü ller & Skakkebaek, 1983) [Figs 1(B) and 2]. Interestingly, the elevated levels of intratesticular testosterone cannot induce meiosis in the foetal and neonatal testis most probably due to the lack of androgen receptor expression in Sertoli cells at those developmental periods (Berensztein et al, 2006;Chemes et al, 2008;Boukari et al, 2009;Rey et al, 2009). Subsequently, the activity of the axis decreases substantially; however, AMH (Aksglaede et al, 2010;Grinspon et al, 2011) and inhibin B production (Bergadá et al, 1999;Andersson & Skakkebaek, 2001) persists being active.…”

Section: Infancy and Childhoodmentioning

confidence: 99%

Male hypogonadism: an extended classification based on a developmental, endocrine physiology‐based approach

et al. 2012

View full text Add to dashboard Cite

SUMMARYNormal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin-like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti-Mü llerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic-pituitary-testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic-pituitary-testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic-pituitary-testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal-onset or postnatal-onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving the gonads and the hypothalamic-pituitary axis.

show abstract

Physiological Androgen Insensitivity of the Fetal, Neonatal, and Early Infantile Testis Is Explained by the Ontogeny of the Androgen Receptor Expression in Sertoli Cells

Abstract: A lack of androgen receptor expression could explain a physiological Sertoli cell androgen insensitivity during fetal and early postnatal life, which may serve to protect the testis from precocious Sertoli cell maturation, resulting in proliferation arrest and spermatogenic development.

Cited by 173 publications

References 19 publications

Endocrinology of the mammalian fetal testis

Endocrinology of the mammalian fetal testis

Expression of testicular androgen receptor in non‐obstructive azoospermia and its change after hormonal therapy

Male hypogonadism: an extended classification based on a developmental, endocrine physiology‐based approach

Contact Info

Product

Resources

About