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Biomedical subjects

J van der Vies

Publications and source records attributed to J van der Vies.

At least 19 recordsLinked to original sources
PubMed1993

Pharmacokinetics of anabolic steroids.

After an anabolic steroid is administered orally there is a rapid increase in its concentration in the blood in the following few hours. Excretion of the compound and its metabolites takes place via the urine and faeces, usually taking several days to completely pass through the system. Parenteral anabolic preparations, such as microcrystal suspensions, implants and solutions of nandrolone esters in a vegetable oil, are absorbed slowly. The absorption of esters from the site of injection is a logarithmic process and depends on the nature of the ester concerned. The absorption rate is slower the longer the fatty acid chain in the ester. The rate of absorption is important regarding the length of the action, and is also relevant for the compound's pharmacodynamic pattern. Metabolism of anabolic steroids takes place mainly in the liver and involves reduction, hydroxylation and the formation of conjugates. The enzymes that bring about these changes and the metabolic pathways involved are similar to endogenous steroids. The presence of high concentrations of metabolites in the bile and in the intestinal tract points to enterohepatic circulation of metabolites. After the administration of slowly-absorbed nandrolone esters the excretion of the metabolites continues for weeks or even months. It is probable that the absorption rate of the esters from the injection depot is the rate-limiting process in the pharmacokinetics of these compounds.

Administration, Oral↗
PubMed1987

Pharmacological studies with (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14).

A novel steroid, (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-yn-3-one (code name Org OD 14), was found to possess concomitant weak oestrogenic, androgenic and progestational activities. The effects observed in other tests, viz. inhibition of ovulation in rats, prevention of bone loss following ovariectomy in rats and restoration of sex drive in castrated male rats, corresponded to this hormonal profile. Studies of the metabolites of Org OD 14 in rats suggested that these are involved in the complex endocrinological properties displayed by the compound.

Androgens↗
PubMed1985

Effects of hyperprolactinemia on the accessory sexual organs of the male rat.

The growth-promoting effect of prolactin on the ventral prostate lobe, the anterior prostate lobe (or coagulating gland), and seminal vesicles has been studied before, during and after puberty in rats up to 5 months of age. Pituitaries from female rats were grafted under the renal capsule of 23-26-day-old male rats. Within 1/2 month substantial (five- to ten-fold) hyperprolactinemia occurred followed by a gradual decline; levels were still high 4 months after grafting. A statistically significant increase in the weight of the seminal vesicles and the ventral and anterior prostate lobes was observed 1 month after implantation. This effect was only maintained for the seminal vesicles during the next 3 months. Hyperprolactinemia did not influence testosterone metabolism. In the ventral prostate lobe, 1 month after grafting, the nuclear androgen receptor content increased, whereas the cytosolic androgen receptor content decreased. These results suggest that the growth-promoting effect of prolactin, on the ventral prostate lobe of the rat, is brought about by an increased translocation of the androgen receptor.

3-Hydroxysteroid Dehydrogenases↗
PubMed1985

Comparison of the receptor binding properties of nandrolone and testosterone under in vitro and in vivo conditions.

Previous in vitro binding studies with androgen receptors in rat seminal vesicles (Toth M. and Zakar T., J. steroid Biochem. 17 (1982) 653-660) have shown that the difference in the effects of nandrolone (N) and testosterone (T) is caused by the fact that 5 alpha-reduction increases the affinity of T and decreases the affinity of N. We confirmed this result using androgen receptors in rat prostate and intact human MCF-7 cells. We also analysed the receptor binding properties of N, T, dihydronandrolone (DHN) and dihydrotestosterone (DHT) in vivo following a combined 2-h infusion of a physiological dose of [3H]T and the same dose of [3H]N in castrated male rats, which permitted a direct comparison of the accumulation of [3H]N, [3H]T, [3H]DHN and [3H]DHT in different sub-cellular fractions of various tissues. There was a considerable accumulation of radioactivity in the liver, but no retention of active compounds. In the prostate there was a preferential retention of [3H]DHT over [3H] DHN in the receptor fractions whereas in thymus, spleen and muscular tissues [3H]N and [3H]T were retained in equal amounts. The kidney showed a preferential retention of [3H]N over [3H]T. The present results explain the relatively strong effect of nandrolone compared to that of testosterone on target tissues devoid of 5 alpha-reductase activity (e.g. muscular tissue) compared to its relatively weak effect on tissues with a relatively high 5 alpha-reductase content (e.g. prostate).

Animals↗
PubMed1985

Implications of basic pharmacology in the therapy with esters of nandrolone.

Experiments in rats have shown that esters of nandrolone injected intramuscularly, are absorbed from the depot according to the kinetics of a first-order reaction. The nature of the fatty acid chain in the ester determines the half-life of the compound in the depot. Once released from the depot, the ester is rapidly hydrolyzed by the esterases in the plasma. As a result, free nandrolone is the pharmacologically active agent whereas its availability to the target organs depends on the half-life time of the ester in the depot. It has been demonstrated that various androgenic target organs respond in a different manner to the changes in the concentration of nandrolone occurring during the period of resorption of the ester. This might explain the dissociation of anabolic from androgenic effects observed with esters of nandrolone. Knowing that the half-life for nandrolone decanoate in man is similar to that in rats, theoretical considerations are given with a number of dosing schemes.

Animals↗
PubMed1984

Oestrogen binding proteins in the female genital tract.

We have estimated the binding characteristics of an oestrogen binding protein in the human vagina and in the human myometrium. The specificities of these binding proteins were analyzed in binding studies using competitors and ligands with different structural features representing the various elements considered to be of importance for binding. The specificity of an oestrogen binding protein in human myometrium was found to be similar to those of oestrogen binding proteins in human breast tumour tissue and in human MCF-7 cells. This specificity was also similar to those of oestrogen receptors in myometrium, endometrium and vagina of the rat. However, the specificity of an oestrogen binding protein in the vagina of postmenopausal patients was different. The vaginal oestrogen-binding protein displayed similar high affinities for 17 beta-oestradiol, 17 alpha-oestradiol and oestriol but low affinity for diethylstilbestrol. The equilibrium dissociation constants for [3H]oestriol and [3H]17 beta-oestradiol were 4.3 X 10(-10) M and 4.0 X 10(-10) M respectively and the concentration of this protein varied between 30 and 170 fmol/mg vaginal cytosol protein. We conclude that the human vagina contains an oestrogen binding protein with characteristics different from those of oestrogen receptors present in myometrium and breast tumour tissue.

Aged↗
PubMed1984

Endocrinological studies with (7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14).

A novel steroid, (7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14), is described which has concomitant weak estrogenic, progestational and androgenic activities. This hormonal profile was demonstrated using various endocrinological tests and the results were evaluated in terms of well-known reference compounds. It has been well established that combinations of estrogens, androgens and progestagens exert positive or synergistic effects on certain target organs, e.g. the hypothalamic-pituitary axis, and antagonistic or complementary effects on others, e.g. on the endometrium. Org OD 14 with estrogenic, androgenic and progestational activities can therefore be expected to induce complex effects on various target organs. This explains the observed effects of the compound on hypothalamic-pituitary axis, bone-loss, endometrium and sexual behaviour.

Anabolic Agents↗
PubMed1983

Binding of progestagens to receptor proteins in MCF-7 cells.

With the aim of finding an explanation for the biological properties of progestagens currently used for contraceptive purposes, we have assessed their specificity for progesterone, androgen and oestrogen receptors in MCF-7 cells. The specificity of progestagens for the progesterone receptors in the cytosol fraction of MCF-7 cells was similar to that for progesterone receptors in human and rabbit myometrial cytosol but different from that for the progesterone receptor in rat myometrial cytosol. At 37 degrees C the relative affinity of 3-keto-desogestrel, the major metabolite of desogestrel, for the progesterone receptor in intact MCF-7 cells was twice that of levonorgestrel and Org 2058, three times that of medroxy-progesterone acetate (MPA), 4.5 times that of norethisterone and 5 times that of progesterone and cyproterone acetate whereas at 4 degrees C in the cytosol fraction of MCF-7 cells exposed to molybdate (nontransformed receptor complexes) 3-keto-desogestrel and Org 2058 displayed similar affinity. The stronger binding of 3-keto-desogestrel in intact cells was due to the higher stability of its complex with the progesterone receptor. At 37 degrees C the relative affinity of 3-keto-desogestrel for the androgen receptor in intact MCF-7 cells was half that of levonorgestrel, similar to that of norethisterone and medroxyprogesterone acetate (MPA) and at least three times higher than that of progestagens with anti-androgenic activity whereas at 4 degrees C in the cytosol fraction exposed to molybdate there was no clear difference between the relative affinities of progestagens with androgenic and anti-androgenic properties. Of the progestagens tested in this study, only norethinodrel displayed measurable but very low relative affinity for the oestrogen receptor in MCF-7 cells. We conclude that the present results of binding studies with intact MCF-7 cells correlate better with the known hormonal properties of progestagens than those obtained with the cytosol fraction exposed to molybdate at 4 degrees C.

Animals↗
PubMed1983

Endocrinological studies with desogestrel.

13-Ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol (Org 2969, desogestrel) is a new progestational steroid which has been developed for application in oral contraceptives. In assays for characteristic progestational effects (McPhail test, McGinty test, Deciduoma test and Antifertilization test) and in tests for inhibition of ovulation, desogestrel is highly active after oral administration and more potent than the structurally related reference compounds norethisterone and levonorgestrel. The same holds for its anti-oestrogenic activity.

Administration, Oral↗
PubMed1982

The pharmacology of oestriol.

The potency ratio of oestriol compared to oestradiol or to ethinyloestradiol depends on the experimental conditions of the test. If a sufficiently high level of oestriol is maintained in a target tissue, either by infusion or by frequent administration, this steroid is capable of eliciting a full oestrogenic effect. At the target tissue, oestriol is a short-acting rather than a weak-acting oestrogen. This explains why certain oestrogenic effects are not observed after a single administration of oestriol or after far-spaced dosings. The short retention time of oestriol in the target tissues makes the oestrogenic effects dependent on the manner of administration of the compound, in particular on the route of administration and on the frequency of dosing.

Animals↗
PubMed1981

A quantitative test for oestrogenic activity using rat endometrium lactate dehydrogenase.

In ovariectomized rats treatment with ethinyloestradiol (EOe) po started 1 week after castration and given for 4 days resulted in an increase of endometrial lactate dehydrogenase per DNA (LDH/DNA). The lambda of the dose-response curve was 0.178. In subsequent experiments EOe was used as a standard and the oestrogenic activity of four steroids given po was compared. The effect of testosterone was studied using oestradiol as a standard. If the activity of EOe is 1, the relative oestrogenic potencies of oestriol succinate, oestradiol decanoate, 11 beta-methyoxymethyl-17 alpha-ethinyl-delta 1,3,5(10)-oestratriene-3,17 beta-diol and 11 beta-methoxymethyl-delta 1,3,5(10)-oestratriene-3,16 alpha,17 beta-triol were 0.074, 0.7, 12.5 and 32, respectively. The results of the test were compared with the relative potencies of these four compounds in two biological tests, viz. the vaginal cornification in ovariectomized adult rats and stimulation of the uterine growth in immature intact rats. The relative oestrogenic potencies as measured by an increase in the endometrial LDH/DNA were in better agreement with those found in the vaginal cornification assay than with those in the uterine growth stimulation test. Testosterone caused no significant changes of LDH/DNA. We conclude that the increase in LDH/DNA in the endometrium of ovariectomized rats can be used as a quantitative assay for oestrogenic potency.

Animals↗
PubMed1977

Oestrogenic activity of oestradiol-decanoate after oral administration to rodents.

Oestradiol-decanoate, dissolved in arachis oil and orally administered to rodents, produces oestrogenic effects. Compared on a molecular basis the ester has 0.1-1.0 times the activity of ethinyl oestradiol, dependent on the species and the parameter studied. The effects of oestradiol-decanoate are less or absent when the oil is omitted. It is likely that absorption of the steroid ester takes place via the intestinal lymphatics in conjunction with the oil.

Administration, Oral↗
PubMed1977

Comparison of the metabolism of testosterone undecanoate and testosterone in the gastrointestinal wall of the rat in vitro and in vivo.

The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat. The major metabolite first appearing during incubation of TU with the small intestine is T. Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.

Animals↗
PubMed1977

Conception, contraception and misconception.

Because of Dr. G. A. Overbeek's interest and contributions in the field of oral contraception a survey is given of present leads and developments in this area. It is concluded that contraceptive preparations known under names such as: once-a-month pill, morning-after pill and post-coitum pill, although desired, do not really exist at the moment. It is further expected that oral contraception based on the inhibition of ovulation will stay with us for many years to come. Better preparations, not exclusively containing oestrogen progestagen combinations but possibly including a non-hormonal pituitary inhibitor as well, might be developed. This will allow better control over the endometrium, and the unwanted effects of the presently used hormonal substances. It is likely that an implantation-inhibiting compound or an abortifacient which acts shortly after implantation will be found. With respect to oral contraception for males it is concluded that, although inhibition of spermatogenesis with drugs is possible, a satisfactory contraceptive treatment for men is not yet available.

Animals↗