Testosterone and estrogen are no longer considered male only and female only hormones. Both hormones are important in both sexes. It was known as early as the 1930's that developmental exposure to a high dose of estrogen causes malformation of the male reproductive tract, but the early formative years of reproductive biology as a discipline did not recognize the importance of estrogen in regulating the normal function of the adult male reproductive tract. In the adult testis, estrogen is synthesized by Leydig cells and the germ cells, producing a relatively high concentration in rete testis fluid. Estrogen receptors are present in the testis, efferent ductules and epididymis of most species. However, estrogen receptor-α is reported absent in the testis of a few species, including man. Estrogen receptors are abundant in the efferent ductule epithelium, where their primary function is to regulate the expression of proteins involved in fluid reabsorption. Disruption of the α-receptor, either in the knockout (αERKO) or by treatment with a pure antiestrogen, results in dilution of cauda epididymal sperm, disruption of sperm morphology, inhibition of sodium transport and subsequent water reabsorption, increased secretion of Cl-, and eventual decreased fertility. In addition to this primary regulation of luminal fluid and ion transport, estrogen is also responsible for maintaining a differentiated epithelial morphology. Thus, we conclude that estrogen or its α-receptor is an absolute necessity for fertility in the male.

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Estrogen in the adult male reproductive tract: A review

Androgen receptor function is required for male embryonic sexual differentiation, pubertal development and the regulation of spermatogenesis in mammals. During spermatogenesis, this requirement is thought to be mediated by Sertoli cells and its genetic and pharmacological disruption is manifested in spermatocytes as meiotic arrest. Through studies of a hypomorphic and conditional allele of the androgen receptor (Ar) gene, we have uncovered a dual post-meiotic requirement for androgen receptor activity during male germ cell differentiation. Observations in Ar hypomorphic animals demonstrate that terminal differentiation of spermatids and their release from the seminiferous epithelium is AR dependent and maximally sensitive to AR depletion within the testis. Cell-specific disruption of Ar in Sertoli cells of hypomorphic animals further shows that progression of late-round spermatids to elongating steps is sensitive to loss of Sertoli cell AR function, but that progression through meiosis and early-round spermatid differentiation are surprisingly unaffected.

/pdf/androgen-receptor-function-is-required-in-sertoli-cells-for-5byt7j8be2.pdf

Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids.

The understanding of estrogen's function in the male reproductive tract is limited, and estrogen receptor (ER) localization in the reproductive tract of the adult male rat has not been described. In the present study, ERalpha was localized by immunohistochemistry using ER21 antibody, which recognizes only ERalpha. Strongest immunoreactivity was seen in epithelia of ductuli efferentes and the initial segment of the epididymis. Nuclei of both ciliated and nonciliated cells were positive. The epithelium of the rete testis, and caput, corpus, and cauda epididymides stained less intensely for ERalpha. The vas deferens epithelium was ERalpha-negative. Stromal tissue in the excurrent ducts was also ERalpha-positive. Using 3H-estradiol autoradiography, specific binding of estradiol was seen in nuclei of ductuli efferentes. Estrogen receptor alpha mRNA expression was greatly enhanced in ductuli efferentes compared to other regions of the male tract and was 3.5x greater than in the uterus. For comparison, the presence of ERalpha was determined using reverse transcription-polymerase chain reaction (RT-PCR) amplification. Estrogen receptor beta mRNA was expressed throughout the male tract and in the prostate. These results indicate that all organs in the male excurrent ductal system of the rat express ERalpha and are potential targets of estrogen. However, the ductuli efferentes are the site of the most intense ERalpha expression. The role of ERbeta remains to be determined, but its expression appears ubiguitous in the male tract.

Estrogen Receptor (α and β) Expression in the Excurrent Ducts of the Adult Male Rat Reproductive Tract

https://www.fertstert.org/article/S0015-0282(02)04679-4/pdf

Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial

Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.

Hormonal control of Sertoli cell metabolism regulates spermatogenesis

In an effort to evaluate the effect of hCG/human menopausal gonadotropin (hMG) treatment on semen parameters in normogonadotropic men suffering from oligospermia, a double blind, placebo-controlled study was conducted After 2 basal examinations of seminal parameters and reproductive hormones, 39 men were recruited for the trial Nineteen men, allocated randomly to the active drug group, received im injections of 2500 IU hCG twice a week in combination with 150 IU hMG three times a week for 13 weeks, while 20 men were treated, following the same injection schedule, with NaCl only After the 13-week treatment period, follow-up examination was performed, followed by 3 additional examinations at 4-week intervals Of those men receiving hCG-hMG, 2 induced pregnancies in their wives, while no pregnancies were reported in the placebo group Sperm concentrations, the percentages of motile sperm, and the proportions of normally formed spermatozoa, however, were similar in the 2 groups at all times It was not pos

Gunter Schleicher

Papers

Treatment of Severe Oligospermia with Human Chorionic Gonadotropin/Human Menopausal Gonadotropin: A Placebo-Controlled, Double Blind Trial

Differentiation between androgen and estrogen receptor mediated effects of testosterone on FSH using androgen receptor deficient (Tfm) and normal mice