Progestin and antiprogestin interactions with progesterone receptors in human myomas.

Progesterone receptors (PRs) in human fibromyomata (myomas) and normal myometrium were characterized by gel filtration, sucrose gradient sedimentation analysis, isoelectrofocusing and ligand specificity. The PR population in myoma tissues, 1242 +/- 505 fmol/mg protein, was 3-fold higher than normal myometrial tissues under similar hormonal milieu. The increased PR concentration in myomas appears to be of potential importance in physiopathology of fibromyoma.

Copper intravas device (IVD) and male contraception.

An alternative method of male contraception is crucial at this stage of increasing population in the developing world. A non-obstructive, non-hormonal, reversible method of male contraception would find acceptance in oriental communities. Our experience with copper IVD in small animals has been encouraging.

Norethindrone in serum after use of an oral contraceptive containing norethindrone acetate.

The availability of norethindrone (NET) in serum was studied in 8 women after daily administration of a combination oral contraceptive pill (MinovlarR) containing 1 mg norethindrone acetate (NETA) and 50 micrograms ethinyl estradiol (EE2) from day 5 to day 25 of the menstrual cycle. The pill was taken daily at 9:30 a.m.

Pharmacokinetics of norethindrone acetate in women after the insertion of a single subdermal implant releasing norethindrone acetate.

The metabolic clearance rate (MCR) of norethindrone acetate (NETA) and norethindrone (NET) levels in plasma were studied after an iv injection of [3H]NETA in three women before and at 1 week, 1, 2 and 6 months following the insertion of a single silastic subdermal implant releasing microquantities of NETA. No significant change in the MCR of NETA was observed at 1 week (459 +/- 72 1/day), 1 month (489 +/- 113 1/day) and 2 months (522 +/- 144 1/day) compared with that of control (525 +/- 108 1/day). However, MCR of NETA showed significant increase in women exposed to continuous presence of NETA for a period of 6 months (608 +/- 121 1/day; P less than 0.

Nuclear progestin receptors in human uterus.

The characteristics and transfer of human uterine progestin receptors from cytosol to nucleus were studied in a cell-free system using [3H]progesterone ([3H]P), [3H]norethindrone ([3H]NET), and [3H]norethindrone acetate ([3H]NETA) as progestin receptor tags. Nuclear receptor binding was observed only in the presence of uterine cytosol. Various prior treatments of uterine cytosol, including warming to 20 C, increasing the salt concentration to 150 mM KCl, or dilution of the cytosol protein concentration to 3 mg/ml, increased the affinity of the receptor for the cell nucleus and thus, facilitated more translocation.

Fluid-filled silastic capsules : a new approach to a more constant steroidal drug delivery system.

A new approach to a more constant steroid delivery system was made in which 7,9 mg of norethisterone acetate was shaped into a cylindrical pellet (diameter 1.47 mm, length 4 mm) and placed inside a silastic capsule (i.d.

Fate of progesterone in the plasma and various tissues of anaesthetized rabbits.

Studies on the metabolism of progesterone in rabbit plasma and tissues during constant infusion of [3H]progesterone revealed a gradual increase in the concentration of progesterone in plasma until a state of equilibrium was attained about 2 h after the start of infusion. The metabolic clearance rate of progesterone was 0.116 l/min and the turn-over time was 0.

Correlation between the serum norethindrone (NET) levels attained after insertion of a silastic implant releasing norethindrone acetate and the endogenous hormones particularly progesterone.

Six normally menstruating women were inserted each with a single silastic implant-D releasing norethindrone acetate (NETA). The levels of endogenous hormones, FSH, LH, E2 and progesterone, were estimated by radioimmunoassay (RIA) procedures in the control and treatment cycles. In addition, the levels of drug in the serum as norethindrone (NET) which is a major metabolite of NETA were also estimated by RIA procedures in the treatment cycles.

Urinary melatonin levels in human breast cancer patients.

Urinary melatonin levels were measured in 10 postmenopausal Indian women suffering from advanced stages of breast cancer and in 9 well-matched women with non-endocrine complaints, mostly uterovaginal prolapse. Urines of each patient were collected over a period of 2-3 days in four 4-hourly intervals from 6 a.m.

Bioavailability of norethindrone in rabbits after administration of norethindrone acetate in single, double and quadruple doses released through subcutaneous silastic implants.

Plasma level of norethindrone (NET) and in vivo release of norethindrone acetate (NETA) were studied in three groups of albino rabbits (5 animals/group) after insertion of one, two and four subcutaneous implants, each containing 40 mg crystalline NETA over a period of 24 weeks. The ratios of the in vivo release rate of steroid were 1, 1.9 and 3.

Progestin receptors in human uterine cytosol.

Progestin(norethindrone and norethindrone acetate)-binding protein, exhibiting characteristics similar to uterine progesterone receptor, has been identified in human uterine cytosol. The progestin receptor was characterized by sedimentation coefficient, 4.2 S; Stokes radius, 39 A; frictional ratio, 1.

In vitro effect of human placental lactogen on steroidogenesis in human placental tissue from early pregnancy.

Studies were carried out with human placental lactogen (hPL) to elucidate its role in regulation of steroidogenesis (progesterone and estrogens) during early pregnancy in humans. Our in vitro studies with early pregnancy placenta under different doses of hPL demonstrated that this hormone could stimulate the synthesis of progesterone as well as estrogens (estrone and estradiol) from their respective precursors.

Further studies of an intravasal copper device in rats.

A 1.5 cm long copper wire caused complete inhibition of fertility in male rats when placed properly in the vasal lumen. The contraceptive effectiveness of the device was directly proportional to the surface area of the device and was non-obstructive.

Plasma levels of 15 (S) 15-methyl-PGF 2 alpha-methyl ester following vaginal administration for induction of abortion in women.

A single suppository containing 3.0 mg 15 (S)15-methyl-PGF2 alpha-methyl ester was administered vaginally in women to terminate mid-trimester pregnancy. Plasma levels of the drug (both methyl ester and free acid forms) were measured at different time intervals using deuterated carriers and gas chromatography-mass-spectrometry.

Pharmacokinetics of norethindrone acetate in women.

The plasma half-life, MCR and plasma metabolite levels at various time intervals have been studied in six women after an intravenous injection of 3H-norethindrone acetate. The disappearance curve due to norethindrone acetate showed an initial rapid disappearance of 3H with an average half-life of 7.5 minutes and a subsequent slow disapperance with a half-life of 51.

Radioimmunoassay of norethindrone : serum levels of norethindrone in lactating women after insertion of a single Silastic implant releasing norethindrone acetate.

A specific radioimmunoassay was developed for the estimation of norethindrone levels in the serum of lactating women. A conjugate of norethindrone-3-BSA was synthesized and antiserum raised against it in rabbits. The antiserum showed high affinity (1.

Interaction of progestins with steroid receptors in human uterus.

Norethindrone (17beta-hydroxy-19-nor-17alpha-pregn-4-en-20-yn-3-one) and norethindrone acetate (17beta-acetoxy-19-nor-17alpha-pregn-4-en-20-yn-3-one) interfered to a varying degree, by competitive inhibition, with the binding of progesterone and oestradiol to respective cytoplasmic receptors in the human uterus. Progesterone binding to 4S macromolecule was saturable and co-specific for progestins. Competitors like norgestrel (17beta-hydroxy-18-methyl-19-nor-17alpha-pregn-4-en-20-yn-3-one), 19-norprogesterone, medroxyprogesterone acetate (17alpha-acetoxy-6alpha-methylpregn-4-ene-3,20-dione) and compound R(5020) (17,21-dimethyl-19-norpregna-4,9-diene-3,20-dione) possessed higher binding affinities for the progestin receptor.