progesterone cream
Sensitivity and specificity of the bioassay of estrogenicity in mammary gland and seminal vesicles of male mice.

Skarda J.

Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Prague.

Young intact (18 days old) and adult castrated males of CBA and C3H/Di mice were used for measuring the estrogenicity on the basis of growth response of mammary epithelial structures and the weight of seminal vesicles. It was demonstrated that heavier young males had disproportionally heavier seminal vesicles (sex steroid-responsive organs) than small animals at day 33 of age (that is on the day when experimental animals were killed and organs dissected). However, the weight of the spleen (sex steroid-nonresponsive organ) was proportionally related to body weight. To minimize variability in hormone responsiveness, all animals were weighed at the age of 18 days and only males weighing 8+/-1 g were used for hormone treatment. The percentage area of mammary fat pad occupiedby mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.01 microg x d(-1). The maximum effective dose of estradiol was 0.1 microg x d(-1) and dose 10 microg x d(-1) of estradiol decreased mammary size to control level (inverted-U-shaped dose-response curve). Progesterone alone stimulated mammary growth only in high doses (500 microg x d(-1) and higher) in young intact males, but had no effect on mammary growth in adult castrated animals. In young intact males, estradiol alone, or progesterone alone decreased the weight of seminal vesicles. No such inhibitory effect of these hormones was noted in adult castrated males. Progesterone acted synergistically with estradiol to produce higher mammary growth compared to that in males treated with estradiol alone. In the presence of progesterone seminal vesicles weight was decreased by estradiol given in such low doses as 0.001 microg x d(-1) of estradiol, which is 10 times lower than that effective in animals treated with estradiol alone. On the other hand, in the adult castrated males a combination of estradiol plus progesterone stimulated seminal vesicles weight. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate (a synthetic steroid exhibiting progestantial and estrogenic activities) and inhibited by both testosterone and cortisol. Estradiol, progesterone, norethindrone acetate, or testosterone did not affect spleen weight and size of mammary lymph nodes.However, cortisol significantly decreased not only spleen weights but also size of mammary lymph nodes. These results showthat simultaneous evaluation of mammary gland growth, seminal vesicles, and the spleen weight in the same animal is suitable for bioassay of estrogenicity as well as for detection of androgenic and antiandrogenic activities.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12234119&dopt=Abstract progesterone, progesterone cream



progesterone cream
Effect of dietary intake on steroid feedback on release of luteinizing hormone in ovariectomized cows.

Rhodes FM, Chagas LM, Clark BA, Verkerk GA.

Dexcel Limited, Private Bag 3221, Hamilton, New Zealand. rhodesf wave.co.nz

This study tested the hypothesis that the decline in pulsatile release of luteinizing hormone (LH), resulting from steroid negative feedback, is greater in animals fed a low, compared with a high, plane of nutrition. Two-year-old cows were ovariectomized and six days later were fed diets to provide 1.5 x maintenance requirements (n = 6, supplemented) or 0.5 x maintenance requirements (n = 6, restricted) (Round 1). Pulsatile release of LH was measured over a 14-h period on the fifth day of feeding these diets (Day 1); at 6 h, all animals were treated with an intravaginal insert containing 1.38 g progesterone, which remained in place until the end of Day 3. Pulsatile release of LH was again measured for 14 h on Day 3; at 6 h, all animals were injected intramuscularly with oestradiol benzoate (ODB; 1 mg per 500 kg live weight). Three days later, this protocol was repeated, in a cross-over design, with cows that were previously restricted now being supplemented and those cows previously supplemented, now restricted (Round 2). Plasma concentrations of progesterone after intravaginal progesterone treatment were 1.01 ng mL(-1) higher in restricted cows compared with supplemented cows (P < 0.001) and were also higher in Round 1 than in Round 2 and on Day 1 than on Day 3 (P < 0.001). Plasma concentrations of oestradiol following injection with ODB did not differ between supplemented and restricted cows (P > 0.1). Dietary intake did not affect mean concentrations of LH, pulse frequency or amplitude during the 6-h period before steroid treatment or the change in these variables following steroid treatment; however, the slope of the decline in concentrations of LH following progesterone treatment was significantly more negative in cows fed restricted diets compared with those fed supplemented diets. In Round 2, mean concentrations of LH were higher preceding, and decreased more following, progesterone treatment compared with the decrease after ODB treatment. In conclusion, acute dietary restriction resulted in a more rapid decline in the release of LH following treatment with intravaginal progesterone, and was associated with higher concentrations of progesterone in plasma.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12729499&dopt=Abstract progesterone, progesterone cream



progesterone cream
Binding of progesterone by human uterine cytosol.

Dyer RD, Sarto GE, Colas AE.

PIP: Equilibrium dialysis or DEAE-cellulose filtration was employed to measure progesterone binding by 100,000 X g supernatants of human myometria from patients undergoing hysterectomy. A significant (p less than .01) correlation in the estimation of high-affinity progesterone binding was found for both techniques. When cortisol competed with tritiated-progesterone for binding receptors, dialysis and filtration assays indicated that the specific binding of progesterone by the cytosols was due to the interaction of progesterone with 2 high-affinity constituents. Cytosols under progestin stimulation had low concentrations of progestin binders, while those under estrogen stimulation had variable binder concentrations. Cytosols from uteri with atrophic endometrium had consistently high concentrations of progestin binders. The experiments showed DEAE-cellulose filtration to be an effective method for evaluating progesterone binding and requires less tissue, less time for incubation, and fewer points for reliable analysis than equilibrium dialysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12259417&dopt=Abstract progesterone, progesterone cream



progesterone cream
[Progesterone and progestins]

[Article in French]

De Lignieres B.

PIP: There are 2 main types of synthetic progestogens: progestogens derived from progesterone and progestogens derived from testosterone. Besides these 2 kinds of progestogens, some steroids have a progestative activity. The characteristics and indications of these various progestogens are examined. The role of progesterone in sterility, contraception and treatment of dysovulation and menopause is described. Progesterone and the various progestogens each have theoretical indications derived from their specific properties. Progesterone represents the most logical treatment for dysovulation, and the safest complement in post-menopause estrogenotherapy. However progesterone is efficient in contraception only for its local effects. Progestogens derived from progesterone are not very suitable for oral contraception and their metabolic side-effects justify their exclusion from estro-progestative contraception. Progestogens derived from testosterone are best adapted to oral contraception although they have some clinical and metabolic side effects. They are inefficient and probably dangerous in the treatment of sterility or during pregnancy. Because of their metabolic side effects, they are not very suitable for the treatment of post-menopause.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12261436&dopt=Abstract progesterone, progesterone cream



progesterone cream
Effect of oestrogens and progesterone alone and in combination on the female rat plasma kininogen concentrations.

Senior J, Whalley ET.

PIP: The effect of estrogens and progesterone alone and in combination on virgin, female rat plasma kininogen levels was studied. Doses of 5 and 10 mcg/kg/day beta-estradiol and 50 and 250 mcg 2,4dimethyl-5,5-diphenyl pent-4-enoic acid sodium salt for 5 days gave a dose response effect. Doses of .5, 2.5, and 5 mg/kg progesterone had no effect on kinin precursor concentration. However, when varying doses of progesterone were used in conjunction with estrogen, a marked increase in kininogen concentrations produced by the estrogens was reduced by, and in proportion to, the dose of progesterone. The effect was more pronounced with the lower doses of estrogen. It appeared that progesterone reduced the increase in kinin precursor produced by the estrogen alone, in proportion to the estrogen/progesterone ration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12276837&dopt=Abstract progesterone, progesterone cream



progesterone cream
[Preclinical research and development of norethisterone]

[Article in French]

Mcguire JL, Hahn DW, Philipps A.

PIP: The numerous studies of norethisterone, alone or combined with ethinyl estradiol, conducted since it came into use in the 1st oral contraceptives (OCs) over 2 decades ago, are described. Inhibition of ovulation is the principal mechanism of action of all current OCs. Administered orally, norethisterone has an ovulation blocking effect 11 to 25 times more potent than levonorgestrel and medroxyprogesterone acetate respectively. Norethisterone and progesterone have equal antiovulatory potency intramuscularly. The cervical mucus of women using OCs containing norethisterone resembles the luteal phase mucus which is hostile to the penetration of sperm. Norethisterone binds to progesterone receptors as readily as doses progesterone, and is active in the classic in vivo assay which measures progestational activity by endometrial stimulation in prepubertal rabbits. Norethisterone, like natural progesterone, maintains pregnancy in ovariectomized rats. It has been agreed for some time that the risk of deleterious effects on lipid metabolism, acne, and other undesirable effects of progestins is proportional to their androgenic activity. The androgenic potency of norethisterone is .008 and that of levonorgestrel is .12 times that of the standard, methyltestosterone. Norethisterone doses required to produce an androgenic reaction in laboratory testing are very high. It can be concluded that at clinical doses, norethisterone has hardly any androgenic effect. Standard bioassays at use levels indicate that norethisterone lacks estrogenic activity, and the same result is obtained in in vitro tests of binding to estrogen receptors. Norethisterone apparently does not modify the serum levels of sex hormone binding globulin (SHBG). In vitro studies have shown that the capacity of norethisterone to bind to SHBG is greater than that of progesterone but less than that of levonorgestrel. In vitro tests in rats demonstrate that norethisterone has an antiestrogenic action 5 times greater than that of progesterone. Norethisterone passes rapidly into the general circulation, attaining maximum plasma concentrations in 1-2 hours. Plasma concentrations vary depending on dose. Oral administration of 1 mg of norethisterone gives plasma levels of 7-30 mcg/ml. About 70% of the dose is abosrbed. 40-50% of the norethisterone administered is excreted in the urine, principally in the form of metabolites, and 20-40% is excreted in the bowel movements. Norethisterone alone or combined with estrogens has been found in longterm studies to have minimal toxic effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12280212&dopt=Abstract progesterone, progesterone cream



progesterone cream
Relationship between steroidogenic acute regulatory protein expression and progesterone production in hen granulosa cells during follicle development.

Johnson AL, Solovieva EV, Bridgham JT.

Department of Biological Sciences, The University of Notre Dame, Indiana 46556, USA. johnson.128 nd.edu

The present studies were conducted to address cellular mechanisms responsible for regulating steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis at maturational stages corresponding to both the time of hen follicle selection, as well as before and after the LH surge in preovulatory follicle granulosa cells. A recently published report has established that mitogen-activated protein (MAP) kinase signaling induced by transforming growth factor alpha (TGFalpha) treatment blocks FSH-induced differentiation and StAR expression in cultured hen granulosa cells, whereas inhibitors of MAP kinase signaling enhance FSH-induced differentiation. The present in vitro studies demonstrate that in addition to MAP kinase signaling, activation of protein kinase C (PKC) blocks both FSH-induced StAR expression and the initiation of progesterone production in prehierarchal follicle granulosa cells, whereas the pharmacologic inhibitor of PKC, GF109203X, potentiates FSH-induced StAR expression and, as a consequence, the initiation of progesterone synthesis. Moreover, we demonstrate in granulosa cells collected from preovulatory follicles that although an acute increase in progesterone production in response to LH treatment requires rapid transcription and translation of StAR, the magnitude of progesterone production is rate-limited by one or more factors other than StAR (e.g., the P450 cholesterol side-chain enzyme). Finally, the rapid turnover of StAR protein, such as occurs following the withdrawal of LH, provides an additional mechanism for the tight regulation of progesterone production that occurs during the hen ovulatory cycle, and explains the rapid loss of steroidogenesis in the postovulatory follicle. In summary, data reported herein support the proposal that paracrine/autocrine factors (including but not necessarily limited to TGFalpha) prevent premature expression of StAR in prehierarchal follicle granulosa cells by more than one receptor-mediated signaling pathway. Furthermore, subsequent to follicle selection into the preovulatory hierarchy, StAR transcription and translation is necessary but not sufficient for the full potentiation of the preovulatory surge of serum progesterone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12297550&dopt=Abstract progesterone, progesterone cream