Insufficient androgen and FSH signaling may be responsible for the azoospermia of the infantile primate testes despite exposure to an adult-like hormonal milieu

Majumdar, Subeer S.; Sarda, Kanchan; Bhattacharya, Indrashis; Plant, Tony M.

doi:10.1093/humrep/des184

Cited by 48 publications

(40 citation statements)

References 50 publications

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“…In males of such species, puberty is triggered by the re-awakening of the hypothalamic GnRH pulse generator after a prolonged period of relative hypoactivity from late infancy until the termination of the juvenile stage of development. Although robust GnRH pulse generator activity during early infancy in boys and male monkeys drives tonic LH and FSH secretion in an adult manner, which in turn leads to secretion of testicular testosterone, spermatogenesis is not initiated because of limited androgen and FSH signaling by the Sertoli cell at this stage of development [157]. Interestingly, by the time the testis acquires the capacity to respond to androgen and FSH stimulation during subsequent pre-pubertal development, a hypogonadotropic state is in place as a result of the turn off of GnRH pulse generator activity, thereby guaranteeing continued gonadal quiescence.…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine control of the onset of puberty

Plant

2015

Frontiers in Neuroendocrinology

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170

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This chapter is based on the Geoffrey Harris Memorial Lecture presented at the 8th International Congress of Neuroendocrinology, which was held in Sydney, August 2014. It provides the development of our understanding of the neuroendocrine control of puberty since Harris proposed in his 1955 monograph [2] that “a major factor responsible for puberty is an increased rate of release of pituitary gonadotrophin” and posited “that a neural (hypothalamic) stimulus, via the hypophysial portal vessels, may be involved.” Emphasis is placed on the neurobiological mechanisms governing puberty in highly evolved primates, although an attempt is made to reverse translate a model for the timing of puberty in man and monkey to non-primate species.

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Section: Discussionmentioning

confidence: 99%

Neuroendocrine control of the onset of puberty

Plant

2015

Frontiers in Neuroendocrinology

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170

144

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“…an early, post-natal, short-lasting rise in gonadotropin) in subjects that most likely did not experience it. From animal models, it appears that there is a pre-pubertal window when FSH can induce Sertoli cell proliferation in immature testis, closed by the subsequent production of androgens from Leydig cells (Majumdar et al, 2012). In line with this hypothesis, FSH treatment in adolescents with pre-pubertal onset HHG, used as a priming before adding hCG, has been demonstrated to be able to induce inhibin B increase, testis growth and pubertal development (Raivio et al, 1997(Raivio et al, , 2007b as well as achievement of spermatogenesis.…”

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confidence: 89%

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

et al. 2014

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SUMMARYA meta-analysis was performed to systematically analyse the results of gonadotropin and GnRH therapy in inducing spermatogenesis in subjects with hypogonadotropic hypogonadism (HHG) and azoospermia. An extensive Medline and Embase search was performed including the following words: 'gonadotropins' or 'GnRH', 'infertility', 'hypogonadotropic', 'hypogonadism' and limited to studies in male humans. Overall, 44 and 16 studies were retrieved for gonadotropin and GnRH therapy, respectively. Of those, 43 and 16 considered the appearance of at least one spermatozoa in semen, whereas 26 and 10 considered sperm concentration upon gonadotropin and GnRH, respectively. The combination of the study results showed an overall success rate of 75% (69-81) and 75% (60-85) in achieving spermatogenesis, with a mean sperm concentration obtained of 5.92 (4.72-7.13) and 4.27 (1.80-6.74) million/ mL for gonadotropin and GnRH therapy, respectively. The results upon gonadotropin were significantly worse in studies involving only subjects with a pre-pubertal onset HHG, as compared with studies involving a mixed population of pre-and post-pubertal onset [68% (58-77) vs. 84% (76-89), p = 0.011 and 3.37 (2.25-4.49) vs. 12.94 (8.00-17.88) million/mL, p < 0.0001; for dichotomous and continuous data, respectively]. A similar effect was observed also upon GnRH. No difference in terms of successful achievement of spermatogenesis and sperm concentration was found for different FSH preparations. Previous use of testosterone replacement therapy (TRT) did not affect the results obtained with gonadotropins. Finally, a higher success rate was found for subjects with lower levels of gonadotropins at the baseline and for those using both human chorionic gonadotropin and FSH. Gonadotropin therapy, even with urinary derivatives, is a suitable option in inducing/restoring fertility in azoospermic HHG subjects. Gonadotropins appear to be more efficacious in subjects with a pure secondary nature (low gonadotropins) and a post-pubertal onset of the disorder, whereas previous TRT does not affect outcome.

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“…Labeling is weak until 4 years of age and increases thereafter [24–27]. In monkeys, androgen binding activity of Sertoli cells cultured from infants is at least 4-fold lower than that for cells cultured at puberty [30]. The lack of AR in the infant human and monkey likely explains the lack of Sertoli sensitivity to the testosterone that is present during the first few months after birth.…”

Section: 1 Ar Expressionmentioning

confidence: 99%

The regulation of spermatogenesis by androgens

Smith

Walker

2014

Seminars in Cell & Developmental Biology

613

356

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Testosterone is essential for maintaining spermatogenesis and male fertility. However, the molecular mechanisms by which testosterone acts have not begun to be revealed until recently. With the advances obtained from the use of transgenic mice lacking or overexpressing the androgen receptor, the cell specific targets of testosterone action as well as the genes and signaling pathways that are regulated by testosterone are being identified. In this review, the critical steps of spermatogenesis that are regulated by testosterone are discussed as well as the intracellular signaling pathways by which testosterone acts. We also review the functional information that has been obtained from the knock out of the androgen receptor from specific cell types in the testis and the genes found to be regulated after altering testosterone levels or androgen receptor expression.

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Insufficient androgen and FSH signaling may be responsible for the azoospermia of the infantile primate testes despite exposure to an adult-like hormonal milieu

Cited by 48 publications

References 50 publications

Neuroendocrine control of the onset of puberty

Neuroendocrine control of the onset of puberty

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

The regulation of spermatogenesis by androgens

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