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.

/pdf/estrogen-in-the-adult-male-reproductive-tract-a-review-4nbka4vuwh.pdf

Estrogen in the adult male reproductive tract: A review

The interstitial tissue of the opossum testis includes interstitial or Leydig cells, macrophages, and small cells which morphologically resemble mesenchymal cells. The latter are thought to give rise to mature interstitial cells. The most prominent feature of the interstitial cell cytoplasm is an exceedingly abundant agranular endoplasmic reticulum. This reticulum is generally in the form of a meshwork of interconnected tubules about 300 to 450 A in diameter, but occasionally it assumes the form of flattened, fenestrated cisternae resembling those of pancreatic acinar cells, except for the lack of ribonucleoprotein particles on the surface of the membranes. The interstitial cells vary considerably in their cytoplasmic density. The majority are quite light, but some appear extremely dense, and in addition usually have a more irregular cell surface, with numerous small pseudopodia. These differences may well reflect variations in physiological state. Cytoplasmic structures previously interpreted as "crystalloids" consist of long bundles of minute parallel tubules, each about 180 A in diameter, which seem to be local differentiations of the endoplasmic reticulum. The mitochondria are rod-shaped, and contain a moderately complex internal membrane structure, and also occasional large inclusions that are spherical and homogeneous. The prominent juxtanuclear Golgi complex contains closely packed flattened sacs and small vesicles. The results of the present study, coupled with biochemical evidence from other laboratories, make it seem highly probable that the agranular endoplasmic reticulum is involved in the synthesis of the steroid hormones produced by the interstitial cell. This finding therefore constitutes one of the first functions of the agranular reticulum for which there is good morphological and biochemical evidence.

/pdf/the-normal-fine-structure-of-opossum-testicular-interstitial-f3p38mbph4.pdf

The normal fine structure of opossum testicular interstitial cells

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the irreversible transformation of androgens into oestrogens and is present in the endoplasmic reticulum of various tissues throughout at least the phylum of vertebrates. The CYP 19 gene is unique and its expression is regulated in a tissue and more precisely in a cell-specific fashion via the alternative use of several promoters located in the first exons. The P450arom has been immunolocalized in germ cells of the mouse, brown bear and rooster. According to age, aromatase activity has been measured in immature and mature rat Leydig cells as well as in Sertoli cells, whereas in the pig, ram and human aromatase is mainly present in Leydig cells. In the adult rat testis, four complementary approaches (RTPCR, in situ hybridization, immunocytochemistry and the tritiated water assay) demonstrate that not only somatic cells but also mature germ cells represent a source of oestrogen synthesis. Taking into account the widespread distribution of oestrogen receptors (ER alpha & ER beta) in testicular cells and the genital tract of the male on the one hand, and the cross-talk between sex steroids and growth factors, and between membrane receptors and nuclear receptors for steroids on the other hand, it is anticipated that understanding of the pathophysiological roles of these 'female' hormones in the male will advance understanding of the hormonal regulation of male reproductive function. One of the future goals is to define oestrogen-targeted genes in the male gonad and indeed, a lot of work is now focused on this specific area in order to clarify the role of oestrogens in the reproductive tract of the male as well as to elucidate the regulation of aromatase gene expression.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2605.1999.00172.x

Sources of oestrogen in the testis and reproductive tract of the male.

Estrogen formation in the brain

The location of the aromatase enzyme in the testes of human subjects ages 3 months to 72 yr was determined immunocytochemically using a monoclonal antibody specific to human aromatase. In addition, an assay was developed to measure aromatase activity in suspensions of cryosections in order to validate the presence and to quantitate the activity of aromatase in the sections. In mature testes, aromatase immunostain was always associated with Leydig cells and was absent from Sertoli cells. Aromatase activity ranged from 0.014-0.55 pmol estrogen per mg/h and was significantly correlated with the immunostain intensity (P < 0.02). Thus, the aromatase activity provided a semiquantitative estimate of the immunoreaction. Activity and immunostain intensity of aromatase did not correlate with increasing age. Rather, the highest levels were measured in four of six testes of men ages 18-20 yr, three of whom also had the strongest immunostain for aromatase. The Leydig cell clusters of these subjects were larger and more prominent than those in the other specimens. A low level of aromatase activity but no immunostain was detected in prepubertal testes. Aromatase was not detected by either method in normal tissue from the testis of a patient with testicular cancer.

Human testicular aromatase: immunocytochemical and biochemical studies

The ability of stallion testis, human term placenta and a human feminizing adrenal cortical carcinoma to convert C14-testosterone to C14-labeled estrogenic steroids has been demonstrated. The relationship between this conversion and the biosynthesis of estrogens by these tissues has been discussed.

Luzmaria Balderas

Papers

Conversion of c14-testosterone to c14-estrogenic steroids by endocrine tissues

Conversion of c14-testosterone to c14-estrogenic steroids by endocrine tissues