Androgen Regulation of Stage-Dependent Cyclin D2 Expression in Sertoli Cells Suggests a Role in Modulating Androgen Action on Spermatogenesis1

The two pituitary gonadotrophins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and in particular LH-stimulated high intratesticular testosterone (ITT) concentration, are considered crucial for spermatogenesis. We have revisited these concepts in genetically modified mice, one being theLH receptor(R)-knockout mouse (LuRKO), the other a transgenic mouse expressing in Sertoli cells a highly constitutively active mutatedFshr(Fshr-CAM). It was found that full spermatogenesis was induced by exogenous testosterone treatment in LuRKO mice at doses that restored ITT concentration to a level corresponding to the normal circulating testosterone level in WT mice, ≈5 nmol/L, which is 1.4% of the normal high ITT concentration. When hypogonadal LuRKO and Fshr-CAM mice were crossed, the double-mutant mice with strong FSH signaling, but minimal testosterone production, showed near-normal spermatogenesis, even when their residual androgen action was blocked with the strong antiandrogen flutamide. In conclusion, our findings challenge two dogmas of the hormonal regulation of male fertility: (1) high ITT concentration is not necessary for spermatogenesis and (2) strong FSH stimulation can maintain spermatogenesis without testosterone. These findings have clinical relevance for the development of hormonal male contraception and for the treatment of idiopathic oligozoospermia.

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Androgen Promotes Differentiation of PLZF+ Spermatogonia pool via Indirect Regulatory Pattern

10.1101/297846 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jingjing Wang ◽

Jinmei Li ◽

Yunzhao Gu ◽

Qin Xia ◽

Weixiang Song ◽

...

Keyword(s):

Germ Cells ◽

Sertoli Cells ◽

Culture System ◽

Molecular Mechanisms ◽

Wilms Tumor ◽

Post Partum ◽

Mice Model ◽

Androgen Action ◽

Wilms Tumor 1

AbstractAndrogen signaling plays a pivotal role in spermatogenesis, but the molecular mechanisms underlying androgen action in this process are unclear. Specifically, it is unknown if the androgen receptor (AR) is expressed in germ cells. Thus it’s interesting to reveal how androgen induces differentiation of spermatogonial progenitor cells (SPCs) in the niche. Here we observed the AR is primarily expressed in pre-spermatogonia of mice 2 days post partum (dpp), absent before spermatogenesis onset, and then expressed in surrounding Sertoli cells. Then we examined a regulatory role of the AR in spermatogenesis using a SPCs-Sertoli cells co-culture system, and demonstrated that androgen negatively regulated Plzf (the gene for stemness maintenance of SPCs). Additionally, we identified Gata2 as a target of AR in Sertoli cells, and demonstrated that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer differentiation signals to SPCs, which was further verified using androgen pharmacological-deprivation mice model. These results demonstrate a regulatory pattern of androgen in SPCs niche in an indirect way via multiple steps of signal transduction.

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Androgen Regulation in Spermatogenesis to Increase Male Fertility

Indonesian Bulletin of Animal and Veterinary Sciences ◽

10.14334/wartazoa.v28i1.1643 ◽

2018 ◽

Vol 28 (1) ◽

pp. 13

Author(s):

Hasbi Hasbi ◽

Sri Gustina

Keyword(s):

Sertoli Cells ◽

Male Fertility ◽

Androgen Receptors ◽

Steroid Hormone ◽

Follicle Stimulating Hormone ◽

Nuclear Receptor Superfamily ◽

Low Concentrations ◽

Androgen Regulation

<p class="00-6Abstrak2Wtz">Male fertility is affected by quantity and quality of sperm which controlled by androgens (testosterone and 5α-dihydrotestosterone) mediated by androgen receptors (AR). Androgen receptors belong to receptor group of steroid hormone and a group of ligand-activated nuclear receptor superfamily. This paper explains androgen hormone and its regulation in spermatogenesis to increase male fertility. Regulation of androgen hormone in spermatogenesis include initiation of spermatogenesis, proliferation and maturation of Sertoli cells, germ cell development, spermatogonia, meiosis, and spermiogenesis. The role of androgen hormone in regulation of spermatogenesis is influenced by AR, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. Disruption of spermatogenesis will cause low male fertility. However, low concentrations of AR, LH and FSH could be enhanced by exogenous gonadotrophine releasing hormone (GnRH), LH, FSH, and testosterone to increase male fertility.</p>

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Direct Action through the Sertoli Cells Is Essential for Androgen Stimulation of Spermatogenesis

Endocrine Reviews ◽

10.1210/edrv.31.2.9994 ◽

2010 ◽

Vol 31 (2) ◽

pp. 261-262

Author(s):

P. J. O'Shaughnessy ◽

G. Verhoeven ◽

K. De Gendt ◽

A. Monteiro ◽

M. H. Abel

Keyword(s):

Germ Cell ◽

Sertoli Cells ◽

Direct Action ◽

Myoid Cells ◽

Animal Group ◽

Cell Numbers ◽

Androgen Treatment ◽

Androgen Action ◽

Testicular Morphology ◽

Stimulation Of

ABSTRACT Androgens act to stimulate spermatogenesis through androgen receptors (ARs) on the Sertoli cells and peritubular myoid cells. Specific ablation of the AR in either cell type will cause a severe disruption of spermatogenesis. To determine whether androgens can stimulate spermatogenesis through direct action on the peritubular myoid cells alone or whether action on the Sertoli cells is essential, we crossed hypogonadal (hpg) mice that lack gonadotrophins and intratesticular androgen with mice lacking ARs either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with testosterone (T) or dihydrotestosterone (DHT) for 7 d and testicular morphology and cell numbers assessed. Androgen treatment did not affect Sertoli cell numbers in any animal group. Both T and DHT increased numbers of spermatogonia and spermatocytes in hpg mice, but DHT has no effect on germ cell numbers in hpg.SCARKO and hpg.ARKO mice. T increased germ cell numbers in hpg.SCARKO and hpg.ARKO mice, but this was associated with stimulation of FSH release. Results show that androgen stimulation of spermatogenesis requires direct androgen action on the Sertoli cells.

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Direct Action through the Sertoli Cells Is Essential for Androgen Stimulation of Spermatogenesis

Endocrinology ◽

10.1210/en.2009-1333 ◽

2010 ◽

Vol 151 (5) ◽

pp. 2343-2348 ◽

Cited By ~ 47

Author(s):

P. J. O'Shaughnessy ◽

G. Verhoeven ◽

K. De Gendt ◽

A. Monteiro ◽

M. H. Abel

Keyword(s):

Germ Cell ◽

Sertoli Cells ◽

Direct Action ◽

Myoid Cells ◽

Animal Group ◽

Cell Numbers ◽

Androgen Treatment ◽

Androgen Action ◽

Testicular Morphology ◽

Stimulation Of

Androgens act to stimulate spermatogenesis through androgen receptors (ARs) on the Sertoli cells and peritubular myoid cells. Specific ablation of the AR in either cell type will cause a severe disruption of spermatogenesis. To determine whether androgens can stimulate spermatogenesis through direct action on the peritubular myoid cells alone or whether action on the Sertoli cells is essential, we crossed hypogonadal (hpg) mice that lack gonadotrophins and intratesticular androgen with mice lacking ARs either ubiquitously (ARKO) or specifically on the Sertoli cells (SCARKO). These hpg.ARKO and hpg.SCARKO mice were treated with testosterone (T) or dihydrotestosterone (DHT) for 7 d and testicular morphology and cell numbers assessed. Androgen treatment did not affect Sertoli cell numbers in any animal group. Both T and DHT increased numbers of spermatogonia and spermatocytes in hpg mice, but DHT has no effect on germ cell numbers in hpg.SCARKO and hpg.ARKO mice. T increased germ cell numbers in hpg.SCARKO and hpg.ARKO mice, but this was associated with stimulation of FSH release. Results show that androgen stimulation of spermatogenesis requires direct androgen action on the Sertoli cells.

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CYP26B1 declines postnatally in Sertoli cells independently of androgen action in the mouse testis

Molecular Reproduction and Development ◽

10.1002/mrd.23302 ◽

2019 ◽

Vol 87 (1) ◽

pp. 66-77 ◽

Cited By ~ 2

Author(s):

Nadia Y. Edelsztein ◽

Kenichi Kashimada ◽

Helena F. Schteingart ◽

Rodolfo A. Rey

Keyword(s):

Sertoli Cells ◽

Mouse Testis ◽

Androgen Action

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Androgen regulation of satellite cell function

Journal of Endocrinology ◽

10.1677/joe.1.05976 ◽

2005 ◽

Vol 186 (1) ◽

pp. 21-31 ◽

Cited By ~ 72

Author(s):

Yue Chen ◽

Jeffrey D Zajac ◽

Helen E MacLean

Keyword(s):

Satellite Cell ◽

Satellite Cells ◽

Cell Activation ◽

Cell Function ◽

Dependent Manner ◽

Androgen Treatment ◽

Androgen Action ◽

Androgen Regulation ◽

And Function

Androgen treatment can enhance the size and strength of muscle. However, the mechanisms of androgen action in skeletal muscle are poorly understood. This review discusses potential mechanisms by which androgens regulate satellite cell activation and function. Studies have demonstrated that androgen administration increases satellite cell numbers in animals and humans in a dose–dependent manner. Moreover, androgens increase androgen receptor levels in satellite cells. In vitro, the results are contradictory as to whether androgens regulate satellite cell proliferation or differentiation. IGF-I is one major target of androgen action in satellite cells. In addition, the possibility of non-genomic actions of androgens on satellite cells is discussed. In summary, this review focuses on exploring potential mechanisms through which androgens regulate satellite cells, by analyzing developments from research in this area.

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Androgen regulation of the androgen receptor of the quail uropygial gland: application of a [3H]mibolerone exchange assay

Journal of Endocrinology ◽

10.1677/joe.0.1090299 ◽

1986 ◽

Vol 109 (3) ◽

pp. 299-306 ◽

Cited By ~ 5

Author(s):

Y. Amet ◽

J.-H. Abalain ◽

S. di Stefano ◽

J.-Y. Daniel ◽

K. Tea ◽

...

Keyword(s):

Androgen Receptor ◽

Binding Sites ◽

Androgen Receptors ◽

Sodium Molybdate ◽

Uropygial Gland ◽

Sebaceous Glands ◽

Androgen Action ◽

Androgen Regulation ◽

Exchange Technique

ABSTRACT An exchange assay for androgen receptors in the quail uropygial gland using [3H]mibolerone was established. The most efficient exchange conditions were 3 days of incubation at 15 °C. Under these conditions, androgen receptors were stable in the presence of sodium molybdate, and the exchange of [3H]mibolerone with endogenous testosterone bound to cytosolic or nuclear androgen receptors was maximal. Less than 5% of [3H]mibolerone-binding sites occurred in the extracted nuclear pellets. Using this exchange technique, it was shown that androgen receptors in the uropygial gland of photostimulated male quail or castrated quail treated with testosterone were activated and that their concentrations in both cytosolic and nuclear fractions were increased. These results confirm the androgen dependency of the quail uropygial gland, and show that it is an organ which can be used as a model for the study of androgen action in sebaceous glands. J. Endocr. (1986) 109, 299–306

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Regulation of testicular anti-Müllerian hormone secretion

Acta Endocrinologica ◽

10.1530/eje.0.1350144 ◽

1996 ◽

Vol 135 (2) ◽

pp. 144-152 ◽

Cited By ~ 25

Author(s):

Rodolfo Rey ◽

Nathalie Josso

Keyword(s):

Sertoli Cells ◽

Transcriptional Control ◽

Hormone Secretion ◽

Seminiferous Tubules ◽

Male Fetus ◽

Steroidogenic Factor 1 ◽

Testicular Differentiation ◽

Androgen Withdrawal ◽

Mullerian Ducts ◽

Androgen Regulation

Rey R, Josso N. Regulation of testicular anti-Müllerian hormone secretion. Eur J Endocrinol 1996; 135:144–52. ISSN 0804–4643 Anti-Müllerian hormone (AMH) is a glycoprotein secreted by Sertoli cells from the time of testicular differentiation and is responsible for the regression of Müllerian ducts in the male fetus. The chronology of AMH expression is very important because Müllerian ducts lose their responsiveness a few days after AMH secretion begins, which suggests that the AMH gene is under precise transcriptional control. Steroidogenic factor 1 (SF-1) is the only transcriptional regulator with demonstrated action on AMH expression. Although necessary for AMH expression, SF-1 alone is not sufficient to induce AMH transcription. SRY expression is turned on in Sertoli cells just before AMH expression is initiated, but the effective implication of SRY in AMH regulation remains unclear. During puberty, AMH expression is regulated negatively by androgens and declines dramatically in seminiferous tubules with meiotic development. Low serum AMH levels are observed in both central and gonadotropin-independent precocious puberty, which suggests that gonadotropins do not downregulate AMH at puberty. Serum AMH returns to normal infantile values 3–6 months after treatment. The absence of androgen response elements on the AMH promoter and the slow response to androgen withdrawal suggest that androgen regulation of AMH secretion is indirect. In patients with defects of androgen production or action, serum AMH reaches abnormally high levels in the neonatal and pubertal periods, which suggests a possible stimulatory role for gonadotropins that could be observed only in the absence of suppressive effects of androgens. Rodolfo Rey, INSERM U.293, Ecole Normale Supérieure, 1 rue Maurice Arnoux, 92120 Montrouge, France

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