Significant advances have taken place in our knowledge of the enzymes involved in steroid hormone biosynthesis since the last comprehensive review in 1988. Major developments include the cloning, identification, and characterization of multiple isoforms of 3β-hydroxysteroid dehydrogenase, which play a critical role in the biosynthesis of all steroid hormones and 17β-hydroxysteroid dehydrogenase where specific isoforms are essential for the final step in active steroid hormone biosynthesis. Advances have taken place in our understanding of the unique manner that determines tissue-specific expression of P450aromatase through the utilization of alternative promoters. In recent years, evidence has been obtained for the expression of steroidogenic enzymes in the nervous system and in cardiac tissue, indicating that these tissues may be involved in the biosynthesis of steroid hormones acting in an autocrine or paracrine manner. This review presents a detailed description of the enzymes involved in the biosynthe...

https://www.researchgate.net/profile/Dale_Buck_Hales/publication/8144948_Overview_of_steroidogenic_enzymes_in_the_pathway_from_cholesterol_to_active_steroid_hormones/links/02e7e5249ac2529059000000.pdf

Overview of Steroidogenic Enzymes in the Pathway from Cholesterol to Active Steroid Hormones

Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors alpha and/or beta and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered "male hormones."

Estrogen and spermatogenesis.

THE ability of cells to interact and communicate is a biological phenomenon that developed with the evolution of multicellular organisms. The cell-cell interactions that have evolved are essential for the survival of both simple organisms such as dictyostelium and complex organisms such as mammals. These cellular associations allow an organism to develop capacities that are greater than the simple sum of their individual parts. As early as 1878, Claude Bernard proposed that the “milieu interieur” (i.e. internally produced fluid environment) and a cybernetic-like control system (i.e. cell-cell interactions and communication) in multicellular organisms are needed to adaptively regulate the growth, development, and maintenance of normal tissue function (1, 2). The experimental analysis of cellular interactions was initiated with the investigation of cell aggregation in simple organisms such as sponges (3, 4) and progressed into the areas of embryology (5) and cell biology (6, 7). Analysis of cell biology on ...

Cell-Cell Interactions in the Testis

A review of brain aromatase cytochrome P450

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 hormonal regulation of testicular aromatization and the intratesticular site of estradiol synthesis was investigated in adult rats. To determine testicular aromatization, cell-free homogenates of whole testes, isolated interstitial tissue, and seminiferous tubules were incubated with [3H]testosterone. 3H-Labeled estrogens were isolated and final identity was established by recrystallization of the product with authentic 17β-estradiol or estrone. No 3H-labeled estrogens could be identified in testicular incubations from saline-treated rats. In contrast, similar incubations from rats treated for 6 days with hCG or LH had the capacity to aromatize testosterone to estradiol. Testicular homogenates from rats treated with 4.4 IU hCG/day synthesized 4.76 pg estradiol/mg protein, which represents approximately 280 pg estradiol synthesized/testis during a 3-h incubation. In incubations of cell-free homogenates of isolated testicular compartments from hCG-treated rats, aromatase activity was demonstrated only i...

Induction of Testicular Aromatization by Luteinizing Hormone in Mature Rats

Aromatization of testosterone in Leydig cells purified from mature rat testes was assessed. Leydig cells incubated for 4 hr with increasing concentrations of [3H]testosterone. At saturating concentrations of testosterone, human chorionic gonadotropin (hCG) acutely stimulated aromatization. This stimulation was first observed at 1 hr, an 8-fold increase being found during a 4-hr incubation. The maximal amount of estradiol produced at saturating concentrations of testosterone and hCG was 1.8 ng per 10(6) cells. These results demonstrate that purified Leydig cells have a high capacity for aromatization and that hCG can acutely stimulate aromatization independently of stimulating testosterone synthesis in vitro.

Acute stimulation of aromatization in Leydig cells by human chorionic gonadotropin in vitro.

Aromatization of testosterone to estradiol was assessed in purified Leydig cells of rats 15, 25, and 60-70 days old. Leydig cells obtained after purification by Metrizamide gradient centrifuga- tion were incubated for 4 h with a saturating concentration of (3 HI testosterone (0.6 iM). (3 HI - Estradiol was isolated and final identity established by recrystallization. Aromatization of (3 HI - testosterone to (3 HI estradiol was demonstrated in Leydig cells of all ages. Basal aromatase activity per 106 Leydig cells was highest in Leydig cells of 25-day-old rats, intermediate in Leydig cells of 1 5-day-old"cats, and lowest in Leydig cells of 60-70-day-old rats. At saturating concentrations of (3 HI testosterone, human chorionic gonadotropin or dibutyryl cyclic AMP acutely stimulated aromatization in Leydig cells of 25 and 60-70-day-old rats, but not of 15-day-old rats. A potent competitive inhibitor of aromatase, 7at-(4'-amino)phenylthioandrost-4-ene-3 ,1 7-dione, markedly inhibited estradiol production from testosterone in Leydig cells from all ages studied. These results demonstrate that Leydig cells of immature rats have the capacity for aromatization and that this step in steroidogenesis can be acutely stimulated by hCG and cAMP in Leydig cells of 25 and 60- 70-day-old rats. The similarity in degree of stimulation of aromatization by dibutyryl cyclic AMP and hCG suggests that acute stimulation of aromatization by hCG is mediated by cyclic AMP.

Luis E. Valladares

Papers

Induction of Testicular Aromatization by Luteinizing Hormone in Mature Rats

Acute stimulation of aromatization in Leydig cells by human chorionic gonadotropin in vitro.

Effects of hCG and Cyclic AMP on Aromatization in Purified Leydig Cells of Immature and Mature Rats