Hormone Signaling in the Testis

Smith, Lee B.; Walker, William H.

doi:10.1016/b978-0-12-397175-3.00016-8

Cited by 40 publications

(27 citation statements)

References 647 publications

(574 reference statements)

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“…The progression of spermatogenesis is halted at the round spermatid stage (Fig. 2), in agreement with the known necessity of testosterone to advance it from round to elongating spermatids (1,3). Surprisingly, when we examined testicular histology of 12-month-old LuRKO mice, patches of full spermatogenesis with mature spermatozoa were found despite the persistently very low ITT concentration (20).…”

Section: Testosterone and Spermatogenesis In Lurko Micesupporting

confidence: 81%

“…The corner stone of the hormonal regulation of spermatogenesis is its maintenance by the high intratesticular concentration of testosterone (ITT) (1,2). This is achieved through luteinizing hormone (LH) stimulation of Leydig cell steroidogenesis, after which testosterone activates in paracrine fashion in Sertoli cells the production of an array of other paracrine factors that maintain the differentiation and proliferation of spermatogenic cells (1,2,3). ITT is 50-to 100-fold higher than that present in peripheral circulation (4,5,6), and this high concentration is considered crucial for the maintenance of effective spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

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MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms

Huhtaniemi

2018

European Journal of Endocrinology

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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 the ()-knockout mouse (LuRKO), the other a transgenic mouse expressing in Sertoli cells a highly constitutively active mutated (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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Section: Testosterone and Spermatogenesis In Lurko Micesupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms

Huhtaniemi

2018

European Journal of Endocrinology

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“…Rather it arises from the decreased expression in the brain of peptide hormones relevant for reproduction, i.e., gonadotrophin-releasing hormone (GnRH) from the hypothalamus, and LH and FSH from the pituitary [227]. LH regulates Leydig cells to produce androgen essential for spermatogenesis, while FSH supports the functionality of Sertoli cells [228]. As described above, GALC deficiency also results in accumulation of the very cytotoxic psychosine in the brain with the plausible consequences on the hypothalamus and pituitary dysfunction.…”

Section: Degradation Of Sgg: Significance Of Sgg Homeostasis In Male mentioning

confidence: 99%

Properties, metabolism and roles of sulfogalactosylglycerolipid in male reproduction

Tanphaichitr

Kongmanas

Faull

et al. 2018

Progress in Lipid Research

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Sulfogalactosylglycerolipid (SGG, aka seminolipid) is selectively synthesized in high amounts in mammalian testicular germ cells (TGCs). SGG is an ordered lipid and directly involved in cell adhesion. SGG is indispensable for spermatogenesis, a process that greatly depends on interaction between Sertoli cells and TGCs. Spermatogenesis is disrupted in mice null for Cgt and Cst, encoding two enzymes essential for SGG biosynthesis. Sperm surface SGG also plays roles in fertilization. All of these results indicate the significance of SGG in male reproduction. SGG homeostasis is also important in male fertility. Approximately 50% of TGCs become apoptotic and phagocytosed by Sertoli cells. SGG in apoptotic remnants needs to be degraded by Sertoli lysosomal enzymes to the lipid backbone. Failure in this event leads to a lysosomal storage disorder and sub-functionality of Sertoli cells, including their support for TGC development, and consequently subfertility. Significantly, both biosynthesis and degradation pathways of the galactosylsulfate head group of SGG are the same as those of sulfogalactosylceramide (SGC), a structurally related sulfoglycolipid important for brain functions. If subfertility in males with gene mutations in SGG/SGC metabolism pathways manifests prior to neurological disorder, sperm SGG levels might be used as a reporting/predicting index of the neurological status.

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“…Impairment of the testicular vasculature, for example, the reduction in venous drainage observed in cases of varicocele, causes intratesticular hypoxia and germ cell apoptosis ( 1 ). The vasculature is also instrumental to the endocrine function of the testis because it is the route by which pituitary gonadotropins are delivered to the testis to support T production and spermatogenesis ( 2 ). Conversely, alongside the lymphatic system, the vascular system is important for transport of T to other body systems; a reduced testis and vascular volume is associated with a reduction in circulating T concentrations ( 3 ).…”

mentioning

confidence: 99%

Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice

Rebourcet

Cruickshanks

et al. 2016

Endocrinology

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The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.

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Hormone Signaling in the Testis

Cited by 40 publications

References 647 publications

MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms

MECHANISMS IN ENDOCRINOLOGY: Hormonal regulation of spermatogenesis: mutant mice challenging old paradigms

Properties, metabolism and roles of sulfogalactosylglycerolipid in male reproduction

Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice

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