Biomedical subjects

J de Visser

Publications and source records attributed to J de Visser.

12 recordsLinked to original sources

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

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↗

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

Strategy in drug research. Synthesis and study of the progestational and ovulation inhibitory activity of a series of 11beta-substituted-17alpha-ethynyl-4-estren-17beta-ols.

Using the strategy based on the Hansch method which analyses effects of substituents on biological activity in terms of their hydrophobic, electronic and steric effects we selectively synthesised a series of 11beta-substituted-17alpha-ethynyl-4-estren-17beta-ols that combine ease of synthesis with good discrimination between these factors aiming at finding the compounds with optimum biological activity in that series. The compounds were tested quantitatively in the Clauberg test (rabbit) and the ovulation inhibition test (rat). The differences in biological activity could reasonably be correlated with two steric effects introduced by the 11beta-substituent. These were a change in the overall shape of the 11beta-substituent and the angular methyl group, and direct steric hindrance of the steroid-receptor protein binding. Some exceptions were found possibly due to metabolic conversion of these compounds to the corresponding 11beta-substituted-17alpha-ethynyl-1,3,5(10)-estra-triene-3,17beta-diols.

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↗

PubMed1975

Progesterone-binding proteins: in vitro binding and biological activity of different steroidal ligands.

Progesterone-binding proteins from human, rabbit, sheep and guinea pig myometrial cytosol, all induced with oestradiol, as well as from pregnant guinea pig myometrium and plasma were investigated. The physico-chemical properties of the oestradiol-induced binding proteins were very similar in all the species studied. In all, 63 steroids were tested for their ability to compete with tritiated progesterone for the binding sites on these six proteins and their relative affinities were determined. The studies reveal that the ligand specificities of oestrogen-induced myometrial binding proteins from human, rabbit and sheep are rather similar, whereas that from guinea pig myometrium has different binding characteristics. The properties of the binding proteins from pregnant guinea pig uterus and plasma differ substantially from all of the induced proteins. It is clear from the different physico-chemical characteristics and binding specificities that the oestrogen-induced myometrial protein of the guinea pig is not the same as that which appears in the myometrium and plasma during pregnancy. The binding energies of the well bound progestational compounds were of the order of -12 Kcal/mole, half of which stems from the interaction of the steroid nucleus with the protein. The specific interaction of the protein with the two functional groups, the 3-keto-4-ene system and the acetyl sid chain each contributed-3 Kcal/mole. In the case of the rabbit, sheep and human proteins a 17alpha-ethynyl-17beta-hydroxyl function could replace the acetyl side chain. For a large number of steroids reasonable agreement existed between the degree of binding to the rabbit myometrial protein and in vivo biological activity (Clauberg-McPhail test) in the same species. The data suggest that as far asthe binding aspect is concerned, the rabbit is an appropriate model for assessing the biological activity of compounds under development for human application. The in vitro binding system is also a useful tool to assess whether steroids need to be bio-activated before eliciting a biological response.

Aged↗

PubMed1975

The pharmacology and metabolism of testosterone undecanoate (TU), a new orally active androgen.

Testosterone undecanoate (TU), either dissolved in arachis oil or as micro-crystal suspension, displays androgenic activity on oral administration to rats in the Hershberger test. The solution in arachis oil is more active than the crystal suspension. When [3H]TU is administered orally to rats, most of it is metabolized in the intestinal wall. The majority of the metabolites probably lose their undecanoate group and are absorbed via the portal vein. The non-metabolized [3H]TU and at least two metabolites are absorbed exclusively via the lymphatic system. One of these metabolites has been identified as 5alpha-dihydrotestosterone undecanoate (5alpha-DHTU). TU has no harmful effects on the liver of the rabbits on oral administration.

Animals↗

PubMed1969