Subject(s)
Abortifacient Agents , Embryonic Development/drug effects , Estradiol Congeners/pharmacology , Pregnancy, Animal/drug effects , Prostaglandins/pharmacology , Alkaline Phosphatase/metabolism , Aminoglutethimide/pharmacology , Animals , Cyclofenil/pharmacology , Diethylstilbestrol/pharmacology , Drug Synergism , Estradiol/pharmacology , Estrogen Antagonists , Female , Indomethacin/pharmacology , Organ Size/drug effects , Pregnancy , Progesterone/blood , Progesterone/pharmacology , Prolactin/pharmacology , Pyrrolidines/pharmacology , Rats , Theophylline/pharmacology , Uterus/drug effectsABSTRACT
In orally estrogen-primed animals, four times as much progesterone is required to bring about secretory changes comparable to those obtained following subcutaneous priming. These findings might be interpreted as evidence that: (a) oral estrogen-induced proliferative changes are either different or inadequate, and (b) excess progesterone is conditio sine qua non for the induction of those proliferative changes susceptible of being transformed into secretory ones.
Subject(s)
Endometrium/drug effects , Progesterone/pharmacology , Administration, Oral , Animals , Estradiol/pharmacology , Ethinyl Estradiol/pharmacology , Female , Injections, Subcutaneous , Quinestrol/pharmacology , RabbitsABSTRACT
The potential for compounds with antifertility activity from the reactions of diphenylcyclopropernone (1) and 2, 3-diphenylthiirene 1, 1-dioxide (2) with enamines is described. In certain instances, a marked dissociation of antifertility from estrogenic activity was possible. Two series were studied extensively, one was stilbene amides (7) and the other stilbene amino ketones (8). The latter series (8) afforded several materials from which, on further biological work-up, was singled out compound 21 as a potent antifertility agent in rats and hamsters.
PIP: The antifertility activity from the reactions of diphenylcyclopropene (1) and 2,3-diphenylthiirene 1,1 dioxide (2) with enamines was investigated in laboratory rodents. A considerable dissociation of antifertility from estrogenic activity was observed in certain instances. Stilbene amides (7) and stilbene aminoketones (8) we re extensively studied. The stilbene aminoketone group provided several materials of which compound 21 was found to be a highly potent antifertility agent. The preparation of the materials is described.
Subject(s)
Bridged Bicyclo Compounds/chemical synthesis , Bridged-Ring Compounds/chemical synthesis , Contraceptives, Oral, Synthetic/chemical synthesis , Cyclopropanes , Animals , Bridged Bicyclo Compounds/pharmacology , Contraceptives, Oral, Synthetic/pharmacology , Cricetinae , Dogs , Embryo Implantation/drug effects , Female , Fertility/drug effects , Fetal Death/chemically induced , Fetal Resorption/chemically induced , Magnetic Resonance Spectroscopy , Organ Size/drug effects , Pregnancy , Pseudopregnancy/drug effects , Rabbits , Rats , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Uterus/drug effectsABSTRACT
We have studied several parameters of prostate function in two inbred lines (2.4 and SsLak) of young and old LSH hamsters. These included weight, acid phosphatase, and [3H]testosterone uptake as influenced by age, castration, and androgen treatment. In the hamster, prostatic acid phosphatase concentration was found to vary inversely with androgen levels, contrary to the usual assumption that this enzyme is androgen dependent. Prostatic uptake of tritiated testosterone was enhanced by castration and by treatment of castrates with doses of androgen which induced a moderate increase in gland size. With advancing age, the prostates of LSH hamsters (both strains) became atrophic rather than hyperplastic, in contrast with a previous report (1). This atrophy appeared to be a consequence of decreased testicular function. The LSH hamsters appear to be a suitable model for the study of senescent changes in the male reproductive system.
Subject(s)
Acid Phosphatase/analysis , Prostate/physiology , Testosterone/metabolism , Age Factors , Animals , Castration , Cricetinae , Male , Organ Size , Prostate/drug effects , Seminal Vesicles , Testis , Testosterone/pharmacology , TritiumABSTRACT
AG was administered orally twice daily for 1 or 3 days to six baboons whose duration of pregnancy ranged from 31 to 99 days. Serum progesterone levels were reduced to as little as 3.2% of the initial concentration in one animal and to 20% or less in four of the five remaining baboons. Serum estrogen levels were depressed by 50% or more in three of the four animals in which they were measured. However, pregnancy ensued for at least 3 wk after treatment in all animals. The data suggest that peripheral blood levels of sex steroids may not reflect the critical concentration of hormones required at the uteroplacental juncture for the successful pregnancy maintenance.
Subject(s)
Aminoglutethimide/pharmacology , Estrogens/blood , Progesterone/blood , Abortion, Spontaneous/chemically induced , Aminoglutethimide/adverse effects , Animals , Female , Haplorhini , Papio , PregnancySubject(s)
Pregnancy Complications/physiopathology , Progesterone/blood , Protein Deficiency/physiopathology , Abortion, Spontaneous/etiology , Animals , Estrone/pharmacology , Female , Gestational Age , Hypophysectomy , Ovary/physiology , Pituitary Gland/physiology , Pregnancy , Prolactin/pharmacology , RatsSubject(s)
Abortion, Induced , Prostaglandins/pharmacology , Animals , Cattle , Corpus Luteum/drug effects , Cricetinae , Dose-Response Relationship, Drug , Female , Fetal Death , Follicle Stimulating Hormone/pharmacology , Hypophysectomy , Norethandrolone/pharmacology , Pregnancy , Progesterone/blood , Prolactin/pharmacology , SheepSubject(s)
Arthritis/drug therapy , Edema/drug therapy , Granuloma/drug therapy , Sulfhydryl Compounds/therapeutic use , Animals , Arthritis/chemically induced , Carrageenan , Croton Oil , Cyclophosphamide/therapeutic use , Cysteine/therapeutic use , Dexamethasone/therapeutic use , Disulfides/blood , Edema/chemically induced , Ethylmaleimide/antagonists & inhibitors , Freund's Adjuvant , Glycoproteins/blood , Granuloma/chemically induced , Indomethacin/therapeutic use , Male , Penicillamine/therapeutic use , Rats , Sulfhydryl Compounds/bloodABSTRACT
PIP: The estrogenic properties of estrazinol hydrobromide (EZ), a water-soluble estrogen, were compared with those of Premarin (PR), another water-soluble estrogen preparation consisting of conjugated equine estrogens. Estradiol-17beta, estra-1,3,5(10)-triene-3,17beta-diol (E), and ethinyl estradiol, 17alpha-ethinyl-1,3,5 (10)-estratriene-3,17beta-diol (EE) were used as reference standards. Subcutaneous progesterone (400 mcg) given to rabbits primed with comparable subcutaneous doses of either E or EE produced full secretory changes of the endometrium, while such a transformation could not be elicited in orally primed animals regardless of the estrogen used. The biological profile or orally administered EZ was very similar to that of oral EE and different from oral PR. Howerver, the oral EZ-induced morphological changes of the rabbit endometrium appeared somewhat different from those produced by oral EE. The findings indicated that following oral administration, EZ-induced endometrial transformation is more "normal" and/or adequate than the changes produced by either EE or PR.^ieng
Subject(s)
Azo Compounds/pharmacology , Estrogens/pharmacology , Progesterone/physiology , Administration, Oral , Animals , Azo Compounds/administration & dosage , Biological Assay , Castration , Estrogens/administration & dosage , Estrogens, Conjugated (USP)/pharmacology , Ethinyl Estradiol/pharmacology , Female , Gonadotropins, Pituitary/antagonists & inhibitors , Ovary/physiology , Rabbits , Solubility , Time Factors , Uterus/drug effects , Uterus/physiology , Vagina/drug effects , Vagina/physiologySubject(s)
Growth Hormone/pharmacology , Methandrostenolone/pharmacology , Muscles/drug effects , Prostate/drug effects , Seminal Vesicles/drug effects , Animals , Body Weight/drug effects , Dexamethasone/pharmacology , Growth Hormone/antagonists & inhibitors , Hypophysectomy , Ketones/pharmacology , Male , Methandrostenolone/antagonists & inhibitors , Muscle Development , Organ Size , Pituitary Gland/physiology , Pregnanes/pharmacology , Prostate/growth & development , Rats , Seminal Vesicles/growth & development , Sheep , Swine , Testosterone/antagonists & inhibitors , Testosterone/pharmacologySubject(s)
Androgen Antagonists , Dexamethasone/pharmacology , Methandrostenolone/pharmacology , Muscle Development , Norsteroids/pharmacology , Prostate/growth & development , Seminal Vesicles/growth & development , Testosterone/pharmacology , Animals , Body Weight , Male , Muscles/drug effects , Organ Size , Pelvis , Prostate/drug effects , Rats , Receptors, Drug , Seminal Vesicles/drug effects , Stimulation, ChemicalSubject(s)
Adjuvants, Immunologic , Arthritis/chemically induced , Indomethacin/therapeutic use , Thyroidectomy , Thyroxine/therapeutic use , Triiodothyronine/therapeutic use , Animals , Arthritis/drug therapy , Inflammation/drug therapy , Male , Mycobacterium , Rats , Sulfhydryl Compounds/blood , Thyroid Hormones/physiologySubject(s)
Corticosterone/metabolism , Cresols/administration & dosage , Estrogens/pharmacology , Progesterone/biosynthesis , Reproduction/drug effects , Adrenal Glands/drug effects , Adrenal Glands/metabolism , Animals , Corpus Luteum/metabolism , Cyclohexanes/administration & dosage , Decidua/drug effects , Embryo Implantation/drug effects , Endometrium/drug effects , Female , Fertility/drug effects , Guinea Pigs , Pregnancy , Pregnenolone/metabolism , Progesterone/pharmacology , Pseudopregnancy , Pubic Symphysis/drug effects , Rabbits , Rats , Rats, Inbred Strains , Uterus/injuriesSubject(s)
Adjuvants, Immunologic , Anti-Inflammatory Agents/therapeutic use , Arthritis/chemically induced , Arthritis/drug therapy , Sulfhydryl Compounds/blood , Sulfides/blood , Animals , Benzoates/pharmacology , Hydrogen-Ion Concentration , Inflammation/drug therapy , Injections, Intradermal , Mycobacterium , RatsSubject(s)
Alkaline Phosphatase/metabolism , Decidua/enzymology , Pregnancy , Pseudopregnancy , Alkaline Phosphatase/blood , Animals , Castration , Electrophoresis , Embryo Implantation/drug effects , Endometrium/enzymology , Enzyme Activation , Estradiol/pharmacology , Estrogens/pharmacology , Ethanol/pharmacology , Female , Folic Acid Antagonists/pharmacology , Glucuronidase/metabolism , Medroxyprogesterone/pharmacology , Nucleic Acids/biosynthesis , Progesterone/pharmacology , Progesterone/physiology , Protein Biosynthesis , Rats , Time Factors , Uterus/enzymologySubject(s)
Ethers/pharmacology , Nandrolone/pharmacology , Animals , Castration , Female , Gonadotropins, Pituitary/metabolism , Male , Organ Size , Ovulation/drug effects , Pregnancy , Pregnancy, Animal/drug effects , Prostate/anatomy & histology , Rats , Sex Determination Analysis/drug effects , Stimulation, Chemical , Uterus/anatomy & histologySubject(s)
Estranes/metabolism , Ethinyl Estradiol/metabolism , Milk/metabolism , Animals , Brain/metabolism , Carbon Isotopes , Chromatography , Chromatography, Thin Layer , Female , Lactation , Pregnancy , Rats , TritiumABSTRACT
PIP: An orally active progestagen, 17 alpha-ethynyl-19-nor-testosterone-17 beta-acetate-3-cyclopeotyl enol-ether (ENTACP) was found to be a potent antiestrual and contraceptive agent in rats. It was evaluated with respect to: 1) progestational activity, 2) pregnancy maintenance, 3) androgenic activity, 4) masculinization of female fetuses, 5) uterotropic activity, 6) effect on adrenal and adrenocortical function, 7) effect on organs and body weight, 8) effect on pregnancy, 9) storage in body fat. ENTACP was twice as effective in producing secretory changes of the endometrium as its parent compound. Pregnancy was not maintained; however, after 22 days, resorption sites were still visable. ENTACP was about 1.5 times as effective as its parent compound in stimulating accessory organs during daily administration. A daily dose of .9 mg orally produced masculinization of the female fetuses, but did not interfere with parturition. Resorption of fetuses occurred more frequently in rats treated with ENTACP than with other compounds tested. ENTACP behaved like an estrogen in stimulating uterine growth. Adrenal weight was significantly increased with ENTACP administration and it reduced the capacity of the adrenal cortical tissue to respond to ACTH. Body weight gain suffered in direct proportion to dose administration. Adrenals, hypophysis, and thyroid increased when expressed in mg/100 gm body weight, and thymus decreased. The oral daily dose of .5 mg/animal from day 1-11 after mating did not prevent pregnancy. At the 5 mg/animal dose nidation was interfered with. Oral administration was not followed by storage of steroid material in body fat.^ieng