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At least 19 recordsLinked to original sources

The effects of castration on adrenal testosterone secretion in men with prostatic carcinoma.

Selective adrenal vein catheterization was done on intact and castrated men with prostatic carcinoma. Adrenal to peripheral venous testosterone gradients were observed in all patients, indicating adrenal production of this hormone. No compensatory adrenal production of testosterone was noted during a 17-month period after orchiectomy. The data suggest that the human adrenal in castrates produces testosterone, which may explain why adrenal ablation can offer palliation in some patients with prostatic carcinoma.

Adrenal Glands

[Demonstration of testosterone secretion by testicular tissue of hypophysectomized boar as affected by HCG in organ culture].

Boar Leydig cells undergo a strong atrophy from 1 to 3 months after hypophysectomy but can be reactivated by the gonadotropin HCG in organ culture conditions. This reactivation which appeared at histological and ultrastructural level was evidenced by the capacity of testicular tissue to synthesize testosterone as judged by radioimmunoassay. Both synthesis in the tissue and release into the medium increased according the incubation time with HCG; the adjonction of 17 alpha-OH-pregneolone to culture medium led to increase the intra and extra-tissular concentration of testosterone.

17-alpha-Hydroxypregnenolone

Pituitary LH and FSH and testosterone secretion in infants with undescended testes.

Twelve male infants with undescended testes (5 bilaterally, 7 unilaterally) were studied between the ages of 1 week and 11 months. As in older pre-pubertal cryptorchid boys, a significant decrease of the LH response to LH-RH test was found, while basal plasma levels of gonadotrophins and FSH response to LH-RH were normal. Plasma testosterone levels were in the normal range, and Leydig cells responded to stimulation by HCG, the degree of this response being significantly and positively correlated to the LH peak elicited by LH-RH. It may be concluded that some early defect of the pituitary-Leydig cell axis is associated with undescended testis.

Chorionic Gonadotropin

Study on the mechanism of SW inhibiting testosterone synthesis in mouse Leydig cells.

BACKGROUND: Swainsonine (SW), the main toxic component of locoweed, can cause livestock poisoning and reproductive damage in male animals; however, the mechanism by which it affects testosterone secretion remains unclear. METHODS: Ten-week-old male C57BL/6 mice were orally administered SW at doses of 0, 0.05, and 0.25 mg/(kg·d) for 28 days. TM3 mouse Leydig cells were treated with SW at concentrations of 0, 1, and 10 nM for 24 h. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on RNA-seq data from mouse testicular tissues to identify differentially enriched pathways between the control and SW-treated groups. Testosterone secretion levels were measured using an enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of steroidogenesis-related genes (StAR, Cyp11a1, Hsd3b2, and Hsd17b3) were detected by qPCR, while the expression of the steroidogenic acute regulatory (STAR) protein was detected by western blotting. AutoDock Vina molecular docking was used to predict the binding affinity between SW and the STAR protein. RESULTS: KEGG analysis revealed a significant enrichment of pathways related to steroid synthesis. In both the mouse model and TM3 cells, SW significantly inhibited testosterone secretion, downregulated the mRNA expression of StAR, Cyp11a1, Hsd3b2, and Hsd17b3, and reduced the protein expression of STAR. Molecular docking analysis revealed multiple potential hydrogen-bond interaction sites between SW and STAR. CONCLUSION: SW downregulates the expression of steroidogenesis-related genes and STAR protein, thereby suppressing testosterone secretion in male mice and TM3 cells.

Swainsonine

Altered metabolism of androgens in elderly men with benign prostatic hyperplasia.

Kinetics of testosterone, dihydrotestosterone (DHT) and 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) were studied in 7 elderly healthy men (ages 61 to 80 years) with benign prostatic hyperplasia (BPH). Clearance rates were determined by the constant infusion technique with labeled testosterone and DHT. Metabolic clearance rate (MCR), conversion ratio (CR), the transfer constants (rho) and production rates (PB) were calculated. Plasma androgens were measured by specific radioimmunoassay. Plasma testosterone was 516 +/- 314 (SD) ng/dl, plasma DHT was 74.6 +/- 19.6 (SD) ng/dl and plasma 3alpha-diol was 16.4 +/- 4.1 (SD) ng/dl. An elevated DHT level in elderly men with BPH wasconfirmed. MCRT was 620 +/- 65 (SD) liter/day and MCRDHT was 393 +/- 50 (SD) liter/day. Both MCRT and MCRDHT in elderly men were significantly lower than in young men. PBT was 3.2 +/- 2.1 (SD) mg/day and PBDHT was 291 +/- 87 (SD)migrogram/day. PBDHT was the same in elderly and young men. DHT production is maintained in elderly men despite reduction of testosterone production. From the data, it was claculated that in contrast to young men where greater than 80% of blood DHT is from secreted testosterone, over 50% in elderly men is derived from secretion or production of DHT by the testis or even more likely the prostate.

Adult

[Effect of neonatal injections of estradiol, testosterone and cryproterone acetate on plasma and testicular testosterone and on the genital system in adult male mice].

On day old male mice received a single injection of oestradiol benzoate, testosterone propionate or cyproterone acetate in order to study their action on testicular development, particularly testosterone secretion. Oestrogenization of newborn males leads, when the animals mature, to a high proportion or cryptorchidism, to atrophy of testes and seminal vesicles, and inhibition of spermatogenesis. Testosterone levels were reduced in the plasma. Testosterone propionate produced moderate reduction of testicular weight but spermatogenesis was not impaired. Plasma testosterone level was reduced. Cyproterone acetate increased significantly testicular testosterone level.

Animals

A novel 2D and 3D model for primary adrenocortical carcinoma of advanced and metastasized stage co-secreting cortisol, aldosterone, testosterone, 18-oxocortisol and 18-hydroxycortisol.

Adrenocortical carcinoma (ACC) is a highly aggressive malignancy with poor survival rates and few treatment options. Preclinical models are indispensable to further strengthen our understanding of disease progression and development of novel therapeutic treatments. Here, we report the establishment of a new cell line named ZUC-1 originating from the resection of an advanced primary ACC and its characterization at the genomic, cellular and molecular level. ZUC-1 cells were successfully propagated as monolayer cultures and three-dimensional spheroids. LC-MS/MS analysis revealed for ZUC-1 cells co-secretion of cortisol, aldosterone and testosterone, and the model represented in direct comparison with other current ACC pre-clinical models furthermore significantly elevated expression of SF-1, CYP11B1 and CYP11B2 genes. Whole genome sequencing identified various mutations in genes linked to DNA repair/stress response, stemness, and also steroidogenesis. Interestingly, ZUC-1 represents genotypic and phenotypic variations that might be of interest beyond ACC, including congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS). Moreover, 18-oxocortisol and 18-hydroxycortisol release was detected in ZUC-1, conditions which are often linked to hyperaldosteronism, but forskolin, potassium and, at higher concentration, angiotensin II modulability of CYP11B2 for this model is retained. ZUC-1 spheroids exhibited furthermore an intra-spheroidal heterogeneous mix of canonical and non-canonical Wnt pathway activation. We conclude that due to its origin and unique geno- and phenotypes, ZUC-1 represents an intriguing model to further gain a basic understanding of adrenal function, the pathogenesis of ACC, but it might be also of interest in the context of CAH and PCOS.

Humans

Some factors affecting testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol secretion by invitro perfused rabbit testes.

Intra-arterial infusion of testosterone-3H gave rise to tritiated dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3beta,17 beta-diol in spermatic venous effluent of the perfused rabbit testis-epididymis. Mass spectrometric measurements confirmed that these four androgens were present in spermatic venous effluent of the perfused rabbit testis-epididymis. Gas liquid chromatographic measurement showed that testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol were secreted in similar amounts by the in vitro perfused and in situ rabbit testis-epididymis results obtained by perfusing the testis minus the epididymis suggested that the bulk of these androgens originate from the catabolism of testosterone within the testis rather than the epididymis. Suprisingly, germinal epithelium destruction by heat failed to alter the testosterone, dihydrotestosterone and 5 alpha-androstan-3 alpha,17 beta-diol secretion by the in vitro perfused rabbit testis. In contrast, the secretion of 5 alpha-androstan-3 beta,17 beta-diol was significantly (P less than 0.05) reduced in the same cryptorchid compared to control testes.

Androstane-3,17-diol

Androgens.

Testosterone is synthesised mainly if not entirely by the leydig cells and secreted episodically with a slight circadian variation. Only the free, nonprotein-bound fraction of the testosterone in the circulation is biologically active. This free testosterone passes into the target cells and is taken up by specific receptors in the muscle. In some other target tissues, testosterone is first reduced to 5alpha-dihydrotestosterone which is then taken up by specific receptors in the cytoplasm and transferred to the nucleus. Anti-androgens appear to act principally by inhibiting this uptake.

Acetates

An apparently direct inhibitory effect of oestrogen on the human testis.

In men suffering from prostatic cancer, i.v. administration of 12 g diethylstilboestrol diphosphate within 20 days resulted in a decrease of the LH serum level to about 50% (P less than 0.05), whereas the total testosterone level decreased to less than 5% (P less than 0.001) and the apparently free testosterone level to less than 2% of the initial values (P less than 0.001). Hence, the "systemic antiandrogenic effect" of oestrogen can be explained (1) by indirect inhibition of testicular androgen secretion via diminution of hypophyseal gonadotrophin secretion, (2) by direct inhibition of testicular androgen secretion and (3) by elevation of the capacity of testosterone binding beta-globulin.

Aged

Study of testicular feedback in male rats using artificial cryptorchidism as a model.

Plasma LH, FSH and testosterone were measured in testosterone-treated and untreated cryptorchid and castrated male rats. Exogenous testosterone prevented the increase in basal LH but not FSH levels seen in the untreated cryptorchids. Increases in plasma LH and FSH in response to LH-RH were greater in the cryptorchid as compared to the control group and this could not be reversed by exogenous testosterone, suggesting that spermatogenesis-related feedback factors regulate LH as well as FSH at the pituitary level in the intact rat. The results were consistent with a reduced but nevertheless significant secretion of inhibin by the cryptorchid testis. Basal plasma testosterone levels and ventral prostate weights were not significantly different from intact animals.

Androgens

[The prehypophyseal-gonadal system in the normal male and in some forms of testicular dyscrinism. Evaluation studies in basic conditions and after stimulation].

The secretion values of the two seric gonadotropins and of plasmatic testosterone have been estimated in a casuistry of normal males subdivided in groups of 8 to 95 years of age, and of primitive and secondary testicular dyschrinia. In one part of this casuistry, normal and primitive hypogonadics, we have estimated the response to the intravenous administration of Gn-RH. Among the results which have been obtained, it appears that physiologic hypogonadism of the elderly is a primary phenomenum, not hypophyso-dependent. In the hypophysiary stimulus test, the response of gonadotropins in those old men moves away from the response of hypogonadics considered, by a behaviour much more similar to that of normal adults, even if delayed and prolonged. In all the cases, normal and pathologic, the response of testosterone is variable, perhaps owing to the relation with the various factor which have been noted.

Adolescent

Serum FSH, LH and prolactin in normal males and patients with prostatic diseases.

Serum FSH, LH and prolactin were measured in fifty-eight normal males between 30 and 80 years of age. At the same time similar estimations were performed on samples taken from 232 patients with benign prostatic hypertrophy (BPH) and twenty-six patients with prostatic carcinoma. The three groups were compared with respect to age, and it was observed that significant rises related to age occurred in the serum levels of FSH, LH and prolactin in normal men after the sixth decade. The patient groups did not differ significantly from each other, or from the normal age-matched population in respect to prolactin and FSH levels. Serum LH in both the carcinoma and BPH patient groups, however, differed significantly from the controls, and remained at the level associated with younger normal males. It is suggested that testosterone metabolites from the prostate exert a negative feedback on pituitary LH secretion.

Adult

Release rate of testosterone and estrogens from polydimethylsiloxane implants for extended periods in vivo compared with loss in vitro.

Release rates of testosterone, estrone, and estradiol placed in chambers made from polydimethylsiloxane (PDS) tubing (Dow Corning "Silastic," 3.35 mm ID x 4.65 mm OD) were studied in 14 freemartin cattle with minimal or non-detectable endogenous hormone secretion, and in 0.9% saline:methanol (1:1) baths shaken at 38 degree C. Eighty-seven implants, varying in length from 2 to 10 cm, were placed in 14 animals for 27 to 235 days. The average release rates +/- standard errors, in microgram/cm/day, were testosterone, 55.9 +/- 2.4, estrone, 12.6 +/- 1.8, and estradiol, 11.1 +/- 1.1. A relatively constant release rate was found over the period of time studied and sufficient steroid remained for potential release over periods exceeding 1 year. The dose of hormone delivered was sufficient to increase mounting activity in testosterone-treated animals and estrual activity in those receiving estrogens. Corresponding release rates in vitro for four 10-cm implants containing either testosterone, estrone, or estradiol were 94.3 +/- 1.9, 15.5 +/- 0.7, and 12.7 +/- 0.6 microgram/cm/day, respectively. The general magnitude of release rate in animals could be predicted from laboratory tests.

Animals