Disruption of nongenomic testosterone signaling in a model of spinal and bulbar muscular atrophy.

As one of the nine hereditary neurodegenerative polyQ disorders, spinal and bulbar muscular atrophy (SBMA) results from a polyQ tract expansion in androgen receptor (AR). Although protein aggregates are the pathological hallmark of many neurodegenerative diseases, their direct role in the neurodegeneration is more and more questioned. To determine the early molecular mechanisms causing motor neuron degeneration in SBMA, we established an in vitro system based on the tetracycline-inducible expression of normal (AR20Q), the mutated, 51 glutamine-extended (AR51Q), or polyQ-deleted (AR0Q) AR in NSC34, a motor neuron-like cell line lacking endogenous AR.

Estrogens in male germ cells.

The biosynthesis of steroids and the production of spermatozoa are two major functions of the mammalian testis which are tightly controlled by gonadotropins and numerous locally produced factors. Among these are the estrogens that are produced within the seminiferous epithelium via the irreversible transformation of androgens (C19) into estrogens (C18) by aromatase. We have recently reported that male germ cells are the new source of estrogens in the testis.

Role of estrogens in spermatogenesis.

Aromatase converts irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various cells of mammalian testes ; at least in rodents, all testicular cells except peritubular cells express aromatase. In testis, high affinity estrogen receptors, ERalpha and/or ERbeta, together with a membrane rapid effect recently described, mediate the effects of estrogens. From the experimental models, in vitro studies and data collected in patients, it is now demonstrated that estrogens play an important role in the testis of vertebrates.

17β-Estradiol regulates cyclin A1 and cyclin B1 gene expression in adult rat seminiferous tubules.

Spermatogenesis, which is the fundamental mechanism allowing male gamete production, is controlled by several factors, and among them, estrogens are likely concerned. In order to enlighten the potential role of estrogen in rat spermatogenesis, seminiferous tubules (ST) from two groups of seminiferous epithelium stages (II-VIII and IX-I) were treated with either 17β-estradiol (E(2)) agonists or antagonists for estrogen receptors (ESRs). In this study, we show that cyclin A1 and cyclin B1 gene expression is controlled by E(2) at a concentration of 10(-9) M only in stages IX-I.

Estrogens: new players in spermatogenesis.

Aromatase that irreversibly transforms androgens into estrogens is present in the smooth endoplasmic reticulum of nearly all cell types in the mammalian testis. In rodents, all testicular cells except for myoid cells express aromatase activity. We have demonstrated the presence of the functional aromatase (transcript or protein, and biological activity) in adult rat germ cells including pachytene spermatocytes and round spermatids.

1α,25-Dihydroxyvitamin D(3) signaling pathways on calcium uptake in 30-day-old rat Sertoli cells.

1α,25-Dihydroxyvitamin D(3) (1,25D(3)) is the active metabolite of vitamin D(3) and the major calcium regulatory hormone in tissues. The aim of this work was to investigate the mechanism of action of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells from 30-day-old rats. Results showed that 10(-9) and 10(-12) M 1,25D(3) increased the rate of (45)Ca(2+) uptake 5 and 15 min after hormone exposure and that 1α,25(OH)(2) lumisterol(3) (JN) produced a similar effect suggesting that 1,25D(3) action occurs via a putative membrane receptor.

1α,25(OH)2-Vitamin D3 stimulates rapid plasma membrane calcium influx via MAPK activation in immature rat Sertoli cells.

It was characterized that the rapid response to 1α,25(OH)(2)-vitamin D(3) (1,25D(3)) on (45)Ca(2+) influx in rat Sertoli cells was mediated by voltage-dependent Ca(2+) channels (VDCCs), PKC, ERK1/2 and p38 MAPK pathways. In primary culture of 10 day-old rat Sertoli cells as well as in the whole testis, the time-course of (45)Ca(2+) influx did not change significantly in basal conditions. However, 1,25D(3) showed stimulatory effect on (45)Ca(2+) influx from 10(-15) to 10(-8) M after 60 s of incubation.

Effect of 1α,25-dihydroxyvitamin D3 in plasma membrane targets in immature rat testis: ionic channels and gamma-glutamyl transpeptidase activity.

1α,25-Dihydroxyvitamin D(3) (1,25D(3)) is critical for the maintenance of normal reproduction since reduced fertility is observed in vitamin D-deficient male rats. The aim of this study was to investigate the effect of 1,25D(3) in 30-day-old rat testicular plasma membrane targets (calcium uptake and gamma-glutamyl transpeptidase (GGTP) activity), as well as to highlight the role of protein kinases in the mechanism of action of 1,25D(3). The results demonstrated that 1,25D(3) induced a fast increase in calcium uptake in rat testis through a nongenomic mechanism of action.

Regulation of aromatase expression by 1α,25(OH)2 vitamin D3 in rat testicular cells.

It is well known that the vitamin D endocrine system is involved in physiological and biochemical events in numerous tissues, especially gut, bone and kidney but also testis. Therefore, in this study the effect and mechanisms of action of 1α,25(OH)(2) vitamin D(3) (1,25D) on aromatase gene expression in immature rat Sertoli cells were evaluated. Vitamin D receptor transcripts were present in immature Sertoli cells as well as in adult testicular germ cells and somatic cells.

Nongenomic and genomic effects of 1α,25(OH)2 vitamin D3 in rat testis.

The steroid hormone 1α,25(OH)(2)-vitamin D(3) (1,25D(3)) regulates gene transcription through a nuclear receptor (VDRnuc) and initiation of rapid cellular responses through a putative plasma membrane-associated receptor (VDRmem). It has been described that successful mating and fertility rates are significantly decreased in vitamin D deficient male rats and a VDR null mutant rodent has decreased sperm count and motility and expresses rare spermatogenesis. Although the Sertoli cells are pointed as the major target of 1,25D(3) in the testis the mechanism of 1,25D(3) action, particularly in Sertoli cells, remains unclear.

Effects of the methanol extract of Basella alba L (Basellaceae) on steroid production in Leydig cells.

In this study, Leydig cells were purified from 70 day-old Sprague Dawley male rats and incubated with 10 and 100 μg/mL of methanol extract of Basella alba (MEBa) for 4 hours followed by the evaluation of cell viability, steroid (testosterone and estradiol) production, and the level of aromatase mRNA. Results showed that MEBa did not affect Leydig cell viability. At the concentration of 10 μg/mL, MEBa significantly stimulated testosterone and estradiol production (p < 0.

Therapeutic effects of soy isoflavones on α-amylase activity, insulin deficiency, liver-kidney function and metabolic disorders in diabetic rats.

Natural estrogens have demonstrated a wide variety of biological activities, which makes them a good candidate for the treatment of diabetes. In vitro, this study evidenced that isoflavones enhanced insulin secretion and inhibited α-amylase activity. In vivo, the findings indicated that soy isoflavones stimulated insulin secretion, increased the hepatic glycogen content and suppressed blood glucose level.

Inhibitory effects of estrogens on digestive enzymes, insulin deficiency, and pancreas toxicity in diabetic rats.

Diabetes mellitus, with its attendant disorders and dysfunctional behaviors, constitutes a growing concern to the population of the world. With this concern in mind, the present study investigated the anti-diabetic and hypolipedimic potential of 17β-estradiol (called E2), particularly in terms of its inhibitory effects on maltase, sucrase, lactase, and lipase activities in the intestine of surviving diabetic rats. The findings revealed that this supplement helped protect the β cells of the rats from death and damage.

Potential protective effect on key steroidogenesis and metabolic enzymes and sperm abnormalities by fenugreek steroids in testis and epididymis of surviving diabetic rats.

The current study showed that the daily oral treatment of fenugreek steroids, designated F(steroids), to diabetic rats during 30 days demonstrated a significant (p < 0.05) decrease of blood glucose level and a considerable increase of the area of insulin-immunoreactive beta-cells in diabetic rats. Interestingly, this study showed that F(steroids) potentially unregulated the key steroidogenesis enzymes such as 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), malic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and glucose-6-phosphate dehydrogenase (G6P-DH) activities as cholesterol rate in testis, which considerably enhanced testosterone and estradiol levels in the plasma of surviving diabetic rats.

Aromatase, oestrogens and human male reproduction.

In most mammalian species aromatase is encoded by a single gene (Cyp19), which contains 18 exons, nine of them being translated. In man, the presence of a biologically active aromatase and oestrogen receptors (ERalpha and ERbeta) has been reported in Leydig cells, and also in immature germ cells and ejaculated spermatozoa. Concerning aromatase, the amount of transcript and enzymatic activity are decreased in immotile compared with motile sperm.

Oestrogens and spermatogenesis.

The role of oestrogens in male reproductive tract physiology has for a long time been a subject of debate. The testis produces significant amounts of oestrogenic hormones, via aromatase, and oestrogen receptors (ERs)alpha (ESR1) and ERbeta (ESR2) are selectively expressed in cells of the testis as well as the epididymal epithelium, depending upon species. This review summarizes the current knowledge concerning the presence and activity of aromatase and ERs in testis and sperm and the potential roles that oestrogens may have in mammalian spermatogenesis.

Aromatase gene expression in immature rat Sertoli cells: age-related changes in the FSH signalling pathway.

Aromatase, the enzyme responsible for the transformation of androgens into oestrogens, is encoded by the cyp19 gene expressed in the testis. The aim of the present study was to analyse the evolution of aromatase gene expression under FSH control in rat Sertoli cells between 10 and 30 days post partum, corresponding to the end of the proliferative period of Sertoli cells, establishment of the blood-testis barrier and acquisition of the mature phenotype. The maximum stimulatory effect of FSH on aromatase gene expression was obtained in 20-day-old rat Sertoli cells, compared with cells from 10- and 30-day-old rats, in parallel with the differentiation of Sertoli cells.

Inhibitory effect of estrogens, phytoestrogens, and caloric restriction on oxidative stress and hepato-toxicity in aged rats.

Objective: To investigate the protective effect of 17beta-estradiol (E2), peganum harmala extract (PHE) administration and calorie restriction (CR) treatment (60%) on oxidative stress and hepato-toxicity in aged rats.

Methods: Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups: normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group.

17 beta-estradiol activates rapid signaling pathways involved in rat pachytene spermatocytes apoptosis through GPR30 and ER alpha.

Aim of the present study was to investigate whether estrogens were able to directly activate rapid signaling pathways controlling spermatogenesis in rat pachytene spermatocytes (PS). Classically, estrogens act by binding to estrogen receptors (ERs) alpha and beta. Recently, it has been demonstrated that rapid estrogen action can also be activated through the G-protein-coupled receptor (GPR)-30.

Immunomodulatory, beta-cell, and neuroprotective actions of fenugreek oil from alloxan-induced diabetes.

Immunological disorders and nephropathy are among the most frequent and serious complications of diabetes mellitus. This shows that fewer infiltrated inflammatory cells evidenced by reverted back to near the normal value of white blood cell, mean corpuscular volume, and lymphocytes counts as interleukin-6 in pancreas. Also, fenugreek oil significantly improved blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group.

1Alpha,25 dihydroxyvitamin D3: therapeutic and preventive effects against oxidative stress, hepatic, pancreatic and renal injury in alloxan-induced diabetes in rats.

Unlabelled: Diabetes mellitus is a major endocrine disorder and a growing health problem in most countries which can be ameliorated by numerous bio-molecules such as 1alpha,25 dihydroxyvitamin D3 [1alpha,25(OH)2VD3]. With this in mind, the current study investigated the therapeutic and preventive effects of 1alpha,25(OH)2VD3 on diabetes and its side effects: toxicity in liver, pancreas and kidneys. Our results show that administration of 1alpha,25(OH)2VD3 in diabetic rats increased the plasmatic insulin level, favored the normal blood glucose levels and normalized the hepatic glycogen concentration.

Mammalian sperm quality and aromatase expression.

In most mammalian species the aromatase is encoded by a single gene (cyp19), which contains 18 exons, 9 of them being translated. In adult rats, together with Leydig cells germ cells represent an additional source of estrogens. The amount of P450arom transcript is threefold higher in pachytene spermatocytes compared to younger cells (spermatogonia-preleptotene spermatocyte) or round spermatids; conversely, aromatase activity is more intense in haploid cells.

Aromatase expression in the normal human adult adrenal and in adrenocortical tumors: biochemical, immunohistochemical, and molecular studies.

Objective: The aromatase enzyme catalyzes the final stage of estrogen biosynthesis pathway from androgens. Its expression in the adrenal is poorly studied except for the rare estrogen-producing adrenocortical tumors. In order to further characterize aromatase expression in the adrenal, we evaluated the aromatase enzyme activity, Cyp19a1 gene expression level, and promoter utilization in normal adrenal tissues and in adrenocortical secreting tumors.

Protective effects of estrogens and caloric restriction during aging on various rat testis parameters.

Aim: To investigate the effects of 17beta-estradiol (E2), Peganum harmala extract (PHE) and caloric restriction (CR) on various testis parameters during aging.

Methods: Twelve month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR (40%).

Results: Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions.