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Biomedical subjects

R R Tremblay

Publications and source records attributed to R R Tremblay.

At least 109 records · Page 6Linked to original sources

Changes in insulin binding in rat testis following testosterone and gonadotrophins administration.

Rat testis membranes possess insulin receptor whose autoregulation is different from conventional insulin target organs. In order to verify the importance of the functional activity of the Leydig cells, different approaches were selected to provoke a resting state of the cells and to measure insulin binding. Testosterone cypionate and LH-RH agonist administration, as well as hypophysectomy, led to a 50% decrease of insulin binding in testis while no effect or a slight increase was observed in hepatic membranes following hypophysectomy. HCG treatments restored insulin binding to its control levels in hypophysectomized animals. These modifications occurred without significant changes in insulin and glucose concentrations. It is concluded that pituitary LH is a key factor in controlling Leydig cell activity as well as its insulin receptor content.

Animals↗

[Partial identification and variations of the cytoplasmic androgen receptor in the rat kidney].

In the course of our studies on the fate of cytoplasmic receptors for androgens in various target organs, such a receptor has been partially characterized in rat kidney cytosol: the high affinity constant, the specificity for testosterone and the formation of a hormone-receptor complex with a 8-10S sedimentation coefficient on sucrose density gradient led us to estimate that this macromolecule was similar to the rat prostate androgen receptor. This receptor is partially occupied by circulating androgens because the number of binding sites increases following castration or hypophysectomy. Constant levels of receptors have been recorded for several months in absence of testosterone. The age and the sex of animals, as well as the functional state of thyroid gland, did not affect the number of binding sites. These receptor characteristics may explain the slight renotrophic action of androgens in rat kidney.

Aging↗

[Measurement of cytoplasmic androgen receptor in compensatory renal hypertrophy in the rat].

In order to determine whether kidney hypertrophy secondary to unilateral nephrectomy was an appropriate model to study cytoplasmic androgen receptor modulation, this receptor was measured three weeks after surgery in intact or castrated animals. Our results demonstrate that the process of kidney hypertrophy is not accompanied by a proportional elevation of the number of androgen receptors and that these receptors are not significantly influenced by the gonadal activity in the rat.

Animals↗

Effect of hormone injections on levels of cytosolic receptors for estrogen, androgen and progesterone in dog prostate.

We have studied the effects of estradiol injections on cytosolic estrogen, androgen and progesterone receptor levels in order to understand the role of this steroid in the induction of prostatic hyperplasia in the dog. Adult mongrel dogs were castrated and were then given injections of estradiol (0.25, 0.8 or 2.5 mg) dissolved in olive oil containing 5% benzyl alcohol on days 0, 2, 5 and 7 after castration. Steroid receptor levels were determined by Scatchard analysis using charcoal assay one day after the last injection. All three receptors were increased maximally with the 0.8 mg dosage when compared with castrated controls. Estradiol binding increased from 89 +/- 10 (mean +/- SEM) to 361 +/- 37 fmol per mg prot., androgen binding from 47 +/- 5 to 123 +/- 11 fmol per mg prot. and progesterone binding from 26 +/- 3 to 211 +/- 36 fmol per mg prot. The small dose of estradiol. (0.25 mg) produced a significant (P less than 0.05) increase of the progesterone receptor levels from 25 +/- 3 to 48 +/- 14 fmol/mg prot. Substitution of estradiol by 5 alpha-androstan-3 beta,17 beta-diol (2.5 or 25 mg) resulted in receptor levels similar to castrated animals. However treatment with 5 alpha-androstan-3 alpha,17 beta-diol (25 mg) alone or in combination with estradiol (0.25 mg) increased significantly the androgen receptor while it decreased the estrogen receptor. These results show that the administration of estradiol at doses used to induce experimental prostate hyperplasia produce measurable effects in the prostate and suggest that the estradiol receptor may be implicated in this phenomenon.

Androstane-3,17-diol↗

Neutral alpha-1,4-glucosidase in human seminal plasma: molecular forms in varicocele and after vasectomy.

Neutral alpha-1,4-glucosidase catalyzes the breakdown of oligosaccharides in several tissues including the reproductive organs, and we have demonstrated the presence of two molecular forms (F1 and F2) of the enzyme in human seminal plasma. The identification of these forms can be achieved by sucrose density gradient analysis and/or electrophoresis in the presence of detergents. Individuals with normal sperm analyses or affected by a varicocele, thus showing normo- or oligoasthenozoospermia, show a similar prevalence of F1 only and F1 + F2 forms, while the presence of F2 alone becomes obvious following vasectomy. In conclusion, molecular forms of the enzyme do not appear to be indicative of the presence of a varicocele, but they may reflect modifications in the secretory function of specific reproductive organs (prostate) or glands (seminal vesicles), as observed in the course of an obstructive abnormality at the epididymal or vas deferens level.

Adult↗

Correlation between L-Carnitine and alpha-1, 4-glucosidase activity in the semen of normal, infertile and vasectomized men.

The semen content of L-carnitine and of alpha 1, 4-glucosidase has been measured in subjects consulting for evaluation of their fertility. A close correlation (r=0.684) was found between both parameters over the range of azoospermia to normal zoospermia. A significant number of patients with oligo or azoospermia displayed normal values of L-carnitine and of alpha-1, 4-glucosidase while approximately 50% showed levels in the low spectrum of vasectomized men. On the basis of these findings, an obstructive pathology at epididymal or vas deferens level was established by vasography and/or bilateral scrotal exploration in 9 patients with azoospermia. These 2 epididymal markers might thus be useful in the hands of the practicing andrologist who has to determine precisely the site of a dysfunction in the reproductive system which leads to infertility.

Biology↗

Binding of methyltrienolone to glucocorticoid receptors in rat muscle cytosol.

Androgen receptor measurements with [3H]-methyltrienolone [17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881)] or [3H]testosterone in vastus lateralis muscle cytosol of intact male rats yielded similar numbers of binding sites. Gonadectomy significantly increased the androgen receptor values, and both steroids gave similar results. The binding of [3H]-testosterone was not affected by adrenalectomy. In contrast, [3H]R1881 binding increased 2-fold after adrenalectomy. Competition experiments as well as sucrose density gradient analysis indicated that R1881, in addition to its binding of the androgen receptor, was also bound to glucocorticoid receptor. These results show that the synthetic androgen R1881 must be used with caution in tissues suspected to contain glucocorticoid receptors.

Adrenalectomy↗

Specific insulin binding sites in rat testis: characterization and variation.

We have found high affinity binding of insulin not only in rat liver and kidney, but also in testis and male sex accessory tissues, prostate, seminal vesicle, and epididymis. We have studied particularly the characteristics of insulin binding in the testis. Membranes sedimenting at 100,000 X g showed the highest binding after 6-20 h of incubation at 0 C. Higher temperatures (15 and 25 C) resulted in lower binding. More than 90% of membrane-bound radioactivity after long incubations at 0 C was eluted at the same position as insulin by Sephadex G-50 chromatography. Membranes could be stored at -80 C for several weeks without loss of activity. Studies on binding specificity showed the following order of competition relative to insulin (100): desalanine insulin (84), proinsulin (2), and desoctapeptide insulin (1). Other peptidic hormones, LH, FSH, PRL, GH, glucagon, and ACTH-(1-24) were totally ineffective. Scatchard representation of the binding data could be resolved into two components with respective affinity constant (Ka) of 1.6 X 10(9) M-1 and 3 X 10(6) M-1. Testicular high affinity binding in adult rats did not vary after 3 days of starvation. However, it increased with age from 1-6 months. By contrast, in rat liver, this type of binding increased after starvation but decreased slightly at 6 months of age. These results show that testicular insulin receptors are similar to those of the liver but may have a different physiological control.

Animals↗

Effect of endocrine manipulations on the levels of cytosolic and nuclear receptors for androgens in dog prostate.

Cytosolic and nuclear androgen receptor levels were determined in dog prostates after castration and after treatment with steroids. The cytosolic androgen receptor levels 1, 5, and 13 days after castration were reduced to 32, 47, and 34 per cent of intact dog levels. We also initiated steroid treatments immediately after castration. The administration three times weekly of either dihydrotestosterone, 5 alpha-androstane-2 alpha, 17 beta-diol (3 alpha-diol), or of a combination of 3 alpha-diol and estradiol resulted after 13 days in a 2 fold increase of cytosolic androgen receptors relative to intact untreated dogs. Androgen receptor levels in 0.5 M KCl nuclear extracts were significantly (P less than 0.01) increased in spontaneously hyperplastic prostates relative to normal prostates. They were also significantly (P less than 0.05) increased in dogs treated with either dihydrotestosterone, 3 alpha-diol, or with a combination of 3 alpha-diol and estradiol but were highly depressed after castration. These results suggest that experimental prostatic hyperplasia produced by the injection of androgens probably occurs via increased androgen receptor levels.

Androstane-3,17-diol↗