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Biomedical subjects

R R Tremblay

Publications and source records attributed to R R Tremblay.

At least 127 records · Page 7Linked to original sources
PubMed1979

Search for progesterone receptors in testes from various animal species.

Using [3H]R5020 as binding probe, we have looked for the presence of progesterone receptors in testis cytosol from a few vertebrate species ranging from the turtles to the humans. In addition, we have tested in the rat several experimental conditions potentially susceptible to induce progesterone receptors. With the exception of chicken, tfm patients and possibly the frogs, progesterone receptors could not be conclusively demonstrated in any of the other animal species tested nor could they be induced in the rat. Surprisingly, they were not present in Stanley-Grumbeck pseudohermaphrodite rats. In chicken testes, the levels of progesterone receptor were variable (3--45 fmol per mg prot.) in the adults and high (87 fmol per mg prot.) in one-day-old animals. The presence of progesterone receptor, a marker of estradiol action in many estrogen-target tissues, seems to be parallel to the capacity of chicken testes for sex reversal under the influence of estrogens. In human tfm, the presence of these receptors could also indicate that the gonads are estrogen-sensitive or that they were so during embryonic life although the nature of estrogenic action is not known.

Animals↗
PubMed1979

New therapeutic approach to the hirsute patient.

Spironolactone, an aldosterone antagonist currently used in the treatment of hypertension, has numerous antiandrogenic side effects. Decreased production rates of testosterone in intact (N = 10) and hirsute (N = 6) women, respectively, were noted after short (7 days) or long-term (6 months) administration of the drug, 25 mg twice daily. A 50% diminution in the urinary 17-ketosteroid excretion was also observed after 6 months of therapy. Assessment of the treatment was done by the patients: a reduction in hair growth rate was initially observed after 3 to 4 months, followed by the appearance of a more downy type of new growth and a decrease in diameter of the hair shaft. It is concluded that this beneficial effect is obtained by a decrease in the testosterone production rate and probably through competitive inhibition of spironolactone and/or canrenone with the androgen receptor in human hair follicles.

17-Ketosteroids↗
PubMed1979

Interaction of spironolactone with rat skin androgen receptor.

Some characteristics of the dorsal skin cytoplasmic androgen receptor (AR) have been studied in male rats. The affinity constant, the binding specificity, and the sedimentation profile of the receptor have been found to be similar to the rat prostate AR. The measurement of the number of binding sites in various hormonal conditions (deprivation) led to the conclusion that this receptor was largely occupied by endogeneous hormones from gonadal and (or) adrenal sources. Administration of spironolactone or canrenone to 7-day-castrated rats was accompanied by a rapid and drastic decrease of available binding sites. This diminution was ascribed to the competitive inhibition of canrenone, the active in vivo metabolite of spironolactone. It is postulated that the antiandrogenic action of spironolactone, at the skin level, is mediated by canrenone which inhibits the formation of specific testosterone and (or) 5 alpha-dihydrotestosterone receptor complex in cytoplasm and consequently in nuclei.

Adrenalectomy↗
PubMed1979

Purification and properties of neutral alpha-1,4 glucosidase from human seminal plasma.

Following a preliminary fractionation of neutral alpha-glucosidase (E.C. 3.2.1.20) from human seminal plasma, we have shown by ion exchange chromatography, Sephadex G-200 filtration, and adsorption chromatography that this alpha-glucosidase activity corresponded to two isoenzymes having the same ability to hydrolyse p-nitrophenyl-alpha-D-glucopyranoside. Both isoenzymes present a heat-stable fraction at 60 degrees C, require the presence of divalent cations in the incubation medium to demonstrate their glycolytic activity, and are inhibited by maltotriose and maltose. They have a molecular weight of approximately 200,000 daltons and different sedimentation profiles on sucrose density gradient. This basic knowledge appears to be the prerequisite for further studies dealing with the importance of such isoenzymes as markers of epididymal function in male fertility.

Carbohydrates↗
PubMed1978

Progestin binding in testes from three siblings with the syndrome of male pseudohermaphroditism with testicular feminization.

We have found a specific binding protein for synthetic progestins 6,7-[3H]methyltrienolone (R1881) and 17,21-dimethyl-19-norpregna-4,9-diene-3,20-dione (R5020) and in the testis cytosol from three "sisters" with the complete form of the testicular feminization syndrome. The binding component sediments in the 8S region of sucrose gradients. It is saturable. The apparent affinity constant (Ka) for R5020 was determined in two cases and found to be 1.8 and 0.6 X 10(8) M-1. The number of binding sites calculated from Scatchard plots is relatively high: 572 and 826 fmol/mg protein. Competition studies indicate that this putative receptor is specific for natural and synthetic progestins but not for 5 alpha-dihydrotestosterone and cortisol. Similar progestin binding could not be found in normal human and rat testes.

Adult↗
PubMed1978

Origin of maltase and variations in infertile men.

A specific assay based on the spectrophotometric determination of the release of p-nitrophenol from p-nitrophenol-alpha-D-glucopyranoside by maltase has been used to measure the activity of the enzyme in seminal plasma and in homogenates of accessory reproductive organs. Specific activity of seminal plasma maltase was 467 muU/mg of proteins in 68 fertile men, decreased significantly in varicocele (296 muU/mg), in azoospermia (246 muU/mg) and in vasectomized patients (62 muU/mg). Application of ion exchange chromatography on DEAE-Sephadex A-50 columns led to the demonstration that maltase activity of seminal plasma and of cytosols from normal reproductive organs was recovered in three different fractions. Maltase activity is thus frequently decreased in infertility.

Adult↗
PubMed1978

P-Nitrophenol-alpha-D-glucopyranoside as substrate for measurement of maltase activity in human semen.

Hitherto, seminal plasma maltase has been measured with maltose as substrate; this method is time consuming and lacks specificity. The use of a synthetic substrate, p-nitrophenol-alpha-D-glucopyranoside, allows accurate and rapid determination of this activity. When maltase is added to the incubation medium (the substrate and reduced glutathione in potassium phosphate buffer, pH 6.8), maintained at 37 degrees C, hydrolysis of the original substrate to p-nitrophenol goes at a constant rate during 4 h. Under optimal conditions of incubation, the Michaelis constant of the reaction, calculated by the Hanes method, was 2.92 +/- 0.84 (SD) X 10(-3) for six different semen samples. Isomaltase appeared to be absent from seminal plasma. The enzyme is stable to freezing and slow thawing and can be stored for at least 26 days at -80 degrees C. Its molecular weight is 259 000. Tris(hydroxymethyl)aminomethane (pH 6.8) exerts a noncompetitive inhibition on the enzyme activity. In 68 men 23 to 45 years old, whose semen analyses were normal, the seminal plasma maltase activity was 467 +/- 135 (SD) mU/g of protein. It was generally decreased in patients with infertility disorders.

Adult↗
PubMed1977

Effect of thyroid state on estradiol-17beta metabolism in the rabbit.

It is well known that the metabolic clearance rate (MCR) of a hormone is influenced highly by the level of its specific binding protein. It was interesting, therefore, to study the metabolism of estradiol-17beta (E2) in an animal model such as the rabbit where there is a lack for a highly specific binding protein for the steroid. The kinetics of the hormone was studied in relation to the thyroid state, namely in rabbits receiving thyroxin or propylthiouracil. In the absence of any significant decrease of the level of the rabbit androgen binding protein (R-ABP), the accelerated MCRE2 and the elevated conversion ratio of estradiol to estrone (CR E2 leads to E1) observed in hyperthyroid rabbits were attributed to the important role of metabolizing enzymes in the liver and/or extrahepatic tissues. In hypothyroid rabbits, while the CR E2 leads to E1 decreased significantly the MCRE2 was not altered.

Animals↗
PubMed1977

Determination of rat muscles androgen-receptor complexes with methyltrienolone.

In the present study, "in vitro" evidences are shown for the existence of a highly active 3alpha-hydroxysteroid dehydrogenase in the crude cytosol of rat muscle homogenates; the use of 5alpha-dihydrotestosterone (DHT) is therefore compromised in receptor binding measurements because of its extensive metabolism. The synthetic anabolic androgen, methyltrienolone (MT) palliates this disadvantage of DHT. Both steroids, as well as testosterone, appear to be bound to an 8 - 8.5 S androgen receptor on sucrose density gradient. The androgen receptor in the vastus and the levator ani bulbocavernosus complex (LA/BC) shows similar association constants, but the number of binding sites in LA/BC is about 5 times higher than in vastus. Otherwise, the total number of muscle androgen receptors seems to be invariant in adult and aged rats. The binding to these macromolecules can thus be measured "in vitro" provided specific and sensitive methods are utilized.

Aging↗
PubMed1977

Apparent saturability of a 4S dihydrotestosterone-binding protein in rat muscle cytosol: role of 3 alpha-hydroxysteroid dehydrogenase and albumin.

In our studies of the binding of steroids in rat skeletal muscles, we have shown the existence of a saturable '4S' dihydrotestosterone-binding protein of low affinity (Kd = 1.16 X 10(-6) M). Competition studies led us to believe that the binding of dihydrotesterone (DHT) was due to 3 alpha-hydroxysteroid dehydrogenase (3 alpha-OHSD) enzyme responsible for the conversion of DHT to androstanediol (Adiol). Indeed, both the binding and the enzymatic activity are inhibited by various 3-keto steroids. In addition, the dissociation constant (Kd) and the Michaelis constant (Km) of the enzyme are similar. However, experiments with ammonium sulfate fractions of the cytosol have shown a partial separation of the binding and of the enzymatic activity. On the other hand, we have established that DHT (3 micrometer) is almost completely metabolized to Adiol during a 2-h incubation of 0 degrees C even in the absence of added coenzymes. Furthermore the '4S' protein binds Adiol more strongly than DHT and this binding is not saturable. Finally the binding behaviour of both DHT and Adiol with either muscle cytosol or rat albumin is similar when subjected to ammonium sulfate fractionation and sucrose density gradient centrifugation. In conclusion, the skeletal muscle 3 alpha-OHSD rapidly metabolizes DHT into Adiol which then binds strongly to a nonspecific binding protein, presumably rat serum albumin. Thus it can be said that the observed saturability of DHT binding is only apparent.

3-Hydroxysteroid Dehydrogenases↗
PubMed1976

Androgen and estrogen binding in rat skeletal and perineal muscles.

Specific in vitro binding of [3H]testosterone (T), 5ALPHA[3H]dihydrotestosterone (DHT), and [3H[estradiol (E2) was demonstrated in the 30 000 X g supernatant (cytosol) of thigh muscles (TM) and of the levator ani - bulbocavernosus muscle complex (LA-BC) by gel filtration through Sephadex G-25 columns. In TM cytosol, T and E2 [are bound with high affinity (Ka = 1.1 X 10(9) M-1, and 2.3 X 10(9) M-1 respectively) whereas DHT binding is of lower affinity (Ka = 5.0 X 10(7) M-1).] In LA-BC cytosol, T, E2, and DHT are bound with high affinity (Ka = 1.9 X 10(9) M-1, 0.3 X 10(9) M-1, and 0.5 X 10(9) M-1, respectively). Competition experiments suggest that the binding of the three hormones (T, E2, and DHT) is due to different proteins. In addition to TM and LA-BC, T and E2 binding was found in other muscles of male and female rats, including gastrocnemius, the pectoralis, diaphragm, and heart.

Animals↗
PubMed1976

Binding of methyltrienolone to various androgen-dependent and androgen-responsive tissues in four animal species.

Comparative sucrose gradient studies of the in vitro binding of dihydrotestosterone (DHT) and of a synthetic androgen, methyltrienolone (R 1881), have been done with the cytosols of various tissues of the rat, mouse, cock and man. With rat prostate cytosol, the amount of R 1881 and DHT binding in the 8-9S region of the gradient was found to be comparable. Specific 8-9S peaks of R 1881 were also found in rat levator ani/bulbocavernosus and skeletal muscles and in the mouse kidney. Only 4-5S peaks could be demonstrated in the cock's comb while DHT under the same conditions showed both 8-9S and 4-5S binding. Binding of R 1881 to the cytosol of the hyperplastic prostate was polydispersed, and showed evidence of the presence of aggregates. Evidence was also found that R 1881 could bind to the progesterone receptor in rat uterus. Our study supports the theory that in a given species the androgen receptors are similar if not identical in all the tissues. The synthetic androgen R 1881 appears to be a useful tool for androgen receptor studies in various animal species provided that the tissue under study contains no progesterone receptor.

Animals↗