progesterone cream
Coactivation of an endogenous progesterone receptor by TIF2 in COS-7 cells.

Hofman K, Swinnen JV, Verhoeven G, Heyns W.

Laboratory for Experimental Medicine and Endocrinology, LEGENDO, Onderwijs en Navorsing, Gasthuisberg, Herestraat 49, Catholic University of Leuven, B-3000 Leuven, Belgium.

Transfection experiments, a powerful tool to study the function of steroid hormone receptors and their coregulators, are often performed in COS-7 cells, because of high transfection efficiencies and expression levels. Here we report on the presence in COS-7 cells of an endogenous steroid hormone receptor, which is highly responsive to progesterone and the synthetic steroids R1881 and ORG2058, but not to 5 alpha-DHT. A 10-fold excess of the progesterone antagonist RU486 abolishes the stimulation by progesterone, while cotransfection with the coactivator TIF2 increases its activity 6- to 7-fold. A comparison of the ligand specificity with transfected androgen or progesterone receptors indicates that the endogenous receptor is a progesterone receptor. Its presence is confirmed by steroid-binding experiments, RT-PCR and Northern blot analysis. Consequently, progesterone receptor function may be studied conveniently in COS-7 cells without cotransfection of receptor, but the endogenous receptor may interfere in studies of ligand specificity and coactivation of cotransfected receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12150973&dopt=Abstract progesterone, progesterone cream



progesterone cream
Synergistic role of progesterone and nitric oxide in the regulation of membrane fluidity of erythrocytes in humans: an electron paramagnetic resonance investigation.

Tsuda K, Kinoshita Y, Nishio I.

Department of Medicine, Wakayama Medical University, Japan. tsudak mail.wakayama-med.ac.jp

BACKGROUND: It has been shown that progesterone may actively participate in the regulation of blood pressure and other cardiovascular regulations. However, the precise mechanism underlying its effects is unclear. METHODS: In the present study, we examined the effects of progesterone on membrane fluidity of erythrocytes in healthy volunteers by means of an electron paramagnetic resonance (EPR) and spin-labeling method. RESULTS: In an in vitro study, progesterone significantly decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes. The finding indicates that progesterone might increase the membrane fluidity and improve the membrane microviscosity of erythrocytes. The effect of progesterone was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP) and a cyclic guanosine monophosphate (cGMP) analogue, 8-bromo-cGMP. In contrast, the change in the membrane fluidity evoked by progesterone was attenuated in the presence of the NO synthase inhibitors, N(G)-nitro-L-arginine-methyl-ester (L-NAME) and asymmetric dimethyl-L-arginine (ADMA). CONCLUSIONS: The results of the present study showed that progesterone increased the membrane fluidity of erythrocytes and ameliorated the rigidity of cell membranes, at least in part, by an NO-dependent mechanism. Furthermore, the data strongly suggest that progesterone might be involved in the regulation of rheological behavior of erythrocytes and have a crucial role in the improvement of microcirculation in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12160193&dopt=Abstract progesterone, progesterone cream



progesterone cream
Estradiol and progesterone regulate oxytocin receptor binding and expression in human breast cancer cell lines.

Amico JA, Rauk PN, Cai HM.

Department of Pharmaceutical Science, University of Pittsburgh, PA, USA. jamico+ pitt.edu

The effects of estradiol (E2) and progesterone on the oxytocin receptor (OTR) were investigated in MCF-7 and Hs 578T human breast cancer cell lines. OTR messenger RNA and protein were identified by reverse transcriptase polymerase chain reaction (PCR) and solution-phase hybridization-RNase protection assay, and Western blot analysis, respectively, in cell lines and in cancerous breast tissue removed from women at mastectomy. Cells were exposed to E2, progesterone, or vehicle (each steroid, 10(-10)-10(-6) M) for 24 h and harvested for extraction of RNA. The OTR PCR product was increased by E2 (10(-7) M, p < 0.05, or 10(-6) M, p < 0.01 vs control) and decreased by progesterone (control vs 10(-7) or 10(-6) M, each p < 0.005). Hs578T cells were cultured in the presence or absence of E2 (10(-6) M) or progesterone (10(-6) M) for 24 h and binding was measured. For the E2-exposed cells, the Kd (p < 0.05), and Bmax (p < 0.01) were higher whereas for the progesterone-treated cells the Kd (p < 0.05) and Bax were lower than control cells. E2 and progesterone not only regulate OTR expression and binding in normal mammary myoepithelium but also in malignant mammary cell lines.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12166628&dopt=Abstract progesterone, progesterone cream



progesterone cream
The pattern of estradiol and progesterone differs in serum and tissue of benign and malignant ovarian tumors.

Lindgren PR, Backstrom T, Cajander S, Damber MG, Mahlck CG, Zhu D, Olofsson JI.

Department of Clinical Sciences/Obstetrics and Gynecology, Umea University Hospital, S-901 85 Umea, Sweden. peter.lindgren obgyn.umu.se

Epidemiological studies have indicated a relationship between gonadal steroid hormones and ovarian cancer. A production of both estradiol and progesterone by ovarian cancers has been demonstrated. The local steroid concentrations and the putative relation to histopathological and clinical condition were investigated herein. Ovarian tissue, ovarian tumor cyst fluid, ovarian vein samples and peripheral serum concentrations of estradiol and progesterone in pre- and post-menopausal women, subdivided into groups with normal ovaries, benign, borderline and malignant ovarian tumors, were quantitatively assessed. Both ovarian tissue concentrations of estradiol and progesterone were more than 100-fold higher than in serum. Based on differences in concentrations between different ovarian tumor groups, the data is not coherent with the previously suggested increased production of estradiol and progesterone in ovarian cancer tissue, since post-menopausal women with ovarian cancer presented lower median tissue hormone levels, most pronounced between malignant and benign tumors; median (25 and 75 percentile) estradiol; 9.40 (6.67-15.50) vs 16.44 (12.49-23.20), p=0.02 and progesterone; 308 (240-575) vs 957 (553-1143) pmol/g wet weight, p<0.01, n=81. Lower concentrations of estradiol, but not progesterone, were found in ovarian cancer tissue, ovarian cyst fluid and peripheral serum in patients with FIGO stages 3 and 4 than in stages 1 and 2. The novel finding of a large ovarian tissue to serum difference of both estradiol and progesterone indicates an important role of ovarian tissue concentrations in tumor biology and raises the question of adequate doses of anti-hormonal therapy in women with ovarian cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12168103&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action.

Straub SG, Sharp GW, Meglasson MD, De Souza CJ.

Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. sgs$ cornell.edu

In rat islets, progesterone caused a prompt concentration-dependent inhibition of glucose-stimulated insulin release with an IC50 of 10 microM at 8.4mM glucose. The inhibition was specific since both testosterone and 17beta-estradiol had no such effect. The degree of inhibition was similar in islets from male and female rats. The inhibition was not blocked in PTX-treated islets thus ruling out the Gi/Go proteins as mediators of the inhibition. Progesterone inhibited both glucose- and BayK-8644-stimulated insulin secretion in HIT-T15 cells and the IC50 vs. 10 mM glucose was also 10 microM. There was no effect on intracellular cyclic AMP concentration in the presence 0.2 and 10 mM glucose. Progesterone decreased [Ca2+]i under all conditions tested. The decrease in [Ca2+]i was due to blockade of the L-type voltage-dependent Ca2+ channels. Under Ca(2+)-free conditions, progesterone did not inhibit the stimulation of insulin release due to the combination of glucose, phorbol ester and forskolin. Thus blockade of Ca2+ entry appears to be the sole mechanism by which progesterone inhibits insulin release. As progesterone covalently linked to albumin had a similar inhibitory effect as progesterone itself, it is concluded that the steroid acts at the outer surface of the beta-cell plasma membrane. These effects would be classified as either AI or AIIb in the Mannheim classification of nongenomically initiated steroid actions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12168772&dopt=Abstract progesterone, progesterone cream



progesterone cream
Inhibition of progestational activity for fertility regulation.

Chatterton RT.

PIP: This review examines a number of areas of postconceptive fertility regulation, focusing on promising new antiprogestational agents. Pregnancy is dependent upon the availability of progesterone for the uterus and its withdrawal results in the breakdown of the secretory endometrium. Its availability can be interferred with at several levels and the new methods which allow for progesterone inhibition must be tested for possible defeminizing properties or for serious side effects. In the evaluation of contragestational agents, several areas must be taken into consideration--assessment of biological activities, dose requirements and mode of action, duration of effects, route of administration, and drug tolerance and side effects. The failure to maintain progesterone in the blood at levels required for pregnancy maintenance may be due to a decrease in progesterone secretion by the ovary or to an increased rate of metabolism and excretion of circulating progesterone. The various substances discussed do either 1 or the other; however even when a compound is known to result in a decrease in the rate of progesterone secretion, the process by which it does this may not be known. Prostaglandins seem to affect myometrial contraction, luteinizing hormone releasing hormones can inhibit steroid production or interfere with LH binding to its receptor, and immunization against hCG is a successful immunological approach to conception. Lithospermic acid is another substance which interferes with gonadotropin support of the ovary and has good potential. Other compounds that interfere with progesterone secretion act to inhibit steroidogenesis in the ovary and placenta; such substances include aminoglutethimide, oxymetholone, trilostane, azastene, and danazol. Another progesterone-suppression method would remove a sufficient amount of progesterone from the body to cause endometrium involution and promote contractility of the myometrium. Progesterone antagonists include ORF 9361, R3434, Anordrin, ORF 3858, and other estrogens, triazole compounds, ORF 5513, trichosanthin, and zoapatanol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12179622&dopt=Abstract progesterone, progesterone cream



progesterone cream
Fecal progesterone analysis by time-resolved fluoroimmunoassay (TR-FIA) for monitoring of luteal function in the sika doe (Cervus nippon centralis).

Takahashi T, Hamanaka S, Imai K, Hashizume K.

Laboratory of Reproductive Biology and Technology, National Institute of Agrobiological Sciences, Ikenodai 2, Kukizaki, Inashiki-gun, Ibaraki 305-8603, Japan.

Fecal progesterone content was measured by time-resolved fluoroimmunoassay (TR-FIA) in the sika doe (Cervus nippon). The total recovery rate of fecal progesterone by twice extraction with diethylether was about 60%. The displacement curve of TR-FIA with serial doses of fecal extract (0.156-5.0 mg feces) was closely parallel to that of the reference standard. Fecal progesterone content was correlated with that of plasma (r=0.829, n=16), but the values were 100-fold higher in feces than in plasma. Fecal progesterone content periodically changed during the breeding season suggesting the estrous cycle in the doe. The fecal progesterone content was higher between the estruses, and decreased after estrus. The time between the onset of estrous signs and the lowest fecal progesterone content was 1-2 days suggesting the time required for hepatic metabolism and intestinal passage. Fecal progesterone content was also decreased around the time of vaginal discharge. The discharge took place within a few days, suggesting a short luteal phase. Not of all decreases in fecal progesterone values were preceded by estrous behavior or vaginal discharge. Fecal progesterone content was further increased in pregnancy rather than in the preceding estrous cycle and the levels were maintained up to term. These results suggest that fecal progesterone measurement is a useful tool for non-invasive analysis of luteal function in the sika doe. The TR-FIA kit, designed for the human hospital market, was shown to be successfully utilized for fecal assay in the sika doe with minor modifications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12185308&dopt=Abstract progesterone, progesterone cream