progesterone cream
A complex role for the progesterone receptor in the response to vascular injury.

Karas RH, van Eickels M, Lydon JP, Roddy S, Kwoun M, Aronovitz M, Baur WE, Conneely O, O'Malley BW, Mendelsohn ME.

Molecular Cardiology Research Institute, New England Medical Center Hospitals Inc., Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Clinical studies of hormone replacement therapy to prevent cardiovascular diseases have heightened interest in the cardiovascular effects of progestins. However, the role of the progesterone receptor (PR) in vascular biology has not been studied in vivo. We studied ovariectomized female PR knockout (PRKO) mice and their wild-type (WT) littermates using the mouse carotid artery injury model. Placebo-treated PRKO mice showed significantly greater vascular medial hypertrophy and vascular smooth muscle cell (VSMC) proliferation in response to vascular injury than did WT mice. Progesterone had no significant effect in the PRKO mice, but worsened the response to injury in WT mice. VSMCs cultured from PRKO mouse aortae were markedly hyperproliferative, and their growth was not affected by progesterone. In contrast to the in vivo findings, progesterone inhibited proliferation of WT-derived VSMCs. Furthermore, reintroduction of PR into PRKO-derived VSMCs using adenoviral methods restored progesterone-mediated inhibition of proliferation to these cells. This effect was reversed by the PR antagonist, RU 486. Thus, the effects of PR and progesterone differ markedly between cultured VSMCs and intact blood vessels. These data demonstrate a direct role for the PR in regulating the response to vascular injury and VSMC proliferation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11518735&dopt=Abstract progesterone, progesterone cream



progesterone cream
Luteinization factor-stimulated steroidogenesis in porcine granulosa cells.

Jezova M, Vrsanska S, Kolena J.

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava. ueenjez savba.sk

Luteinization stimulator (LS), an intrafollicular compound of preovulatory (5-8 mm) follicles, increased both the basal and gonadotropins-stimulated production of progesterone by immature (1-3 mm) granulosa cells. The mechanism by which LS enhance steroidogenesis was investigated by studying the modulation of progesterone biosynthesis from exogenous cholesterol and pregnenolone in cultured porcine granulosa cells in serum-free medium. Progesterone production by cultured granulosa cells was stimulated by FSH, while treatment with 22-OH-cholesterol further enhanced the gonadotropin action. The activity of LS was found in cell conditioned media obtained after 3-day cultivation of preovulatory granulosa cells. Conversion of 22-OH-cholesterol into progesterone by granulosa cells isolated from small follicles was significantly stimulated in the presence LS in culture media. Also, progesterone production by granulosa cells in the presence of pregnenolone was increased considerably. Concomitant treatment with LS led to a further augmentation in progesterone synthesis. Endogenous formation of pregnenolone was inhibited by aminoglutethimide. Thus, LS enhancement of progesterone production in cultured porcine granulosa cells is associated with an increase in the activity of cytochrome P450 cholesterol side-chain cleavage and 3beta hydroxysteroid dehydrogenase enzymes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11519688&dopt=Abstract progesterone, progesterone cream



progesterone cream
Coeliac ganglion adrenergic activity modifies ovarian progesterone during pregnancy: its inter-relationship with LH.

Casais M, Sosa ZY, Rastrilla AM, Aguado LI.

Laboratorio de Biologia de la Reproduccion, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, San Luis (5700), Argentina.

Most of the fibres that constitute the superior ovarian nerve (SON) originate at the neuronal bodies of the coeliac ganglion and innervate rat ovarian stroma cells. The purpose of this work was to study the part played by innervation on ovarian release of progesterone on day 15 and at the end of pregnancy in an integrated in vitro system known as the coeliac ganglion-SON-ovary system. We also investigated, in the same system, whether there is some kind of inter-relationship between the effect of adrenergic agents and LH on progesterone release on day 15 of pregnancy. The coeliac ganglion and the ovary were incubated in separate compartments, linked by the SON. The ovary was immersed in 2 ml buffer solution (ovarian compartment) and the coeliac ganglion was immersed in 2 ml of a different buffer solution (ganglion compartment). Under these conditions, the accumulation of progesterone in the ovarian compartment medium was used as an endpoint. Conditions were standardised on day 15 of pregnancy, when the decrease in the release of ovarian progesterone caused by non-specific stimulation on the ganglion with KCl (56 mM) demonstrated the functional integrity of the system. Neural influence was evaluated by the addition of adrenergic agents at a concentration of 10(-6)M to the coeliac ganglion. On day 15 of pregnancy, noradrenaline and propranolol increased progesterone release while phentolamine diminished it. The existence of ganglionic tone was assessed by analysing progesterone basal levels at different stages of pregnancy. The highest secretion of progesterone was found to take place on day 15, diminishing as pregnancy advanced. In addition, adrenergic neural participation was studied during the physiological luteolysis occurring at the end of pregnancy. Major findings were that noradrenaline increased ovarian accumulation of progesterone on day 19 and decreased it on day 20, while propranolol and phentolamine diminished progesterone release on both days. In additional studies, some neuroendocrine aspects were investigated at a peripheral level. The addition of LH only to the ovarian compartment did not affect progesterone secretion. However, when LH in the ovarian compartment was accompanied by noradrenaline, propranolol or phentolamine in the ganglion compartment, the release of progesterone decreased. It can be concluded that modifications of the neural state of the coeliac ganglion affect ovarian progesterone secretion and the physiology of pregnancy via the SON. The results may confirm that the coeliac ganglion-SON-ovary system provides a direct link between the autonomic nervous system and physiological events during pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11524237&dopt=Abstract progesterone, progesterone cream



progesterone cream
Oestradiol plus progesterone treatment increases serum leptin concentrations in normal women.

Messinis IE, Papageorgiou I, Milingos S, Asprodini E, Kollios G, Seferiadis K.

Department of Obstetrics and Gynaecology, University of Thessalia, Larissa, Greece. messinis med.uth.gr

BACKGROUND: Previous studies have alluded to a role for both oestradiol and progesterone in the secretion of leptin from fat cells in the human, although direct evidence has yet to be obtained. The study aim was to assess serum leptin concentrations in normally cycling women receiving exogenous oestradiol and progesterone. METHODS: Normally cycling women were investigated in an untreated spontaneous cycle (control, n = 10), a cycle treated with oestradiol (oestradiol cycle, n = 10) and a cycle treated with oestradiol plus progesterone (oestradiol+progesterone cycle, n = 6). Oestradiol was given to the women through skin patches on cycle days 2, 3 and 4, and progesterone intravaginally on cycle days 3, 4 and 5. Serum concentrations of leptin, oestradiol, progesterone, FSH and LH were measured in daily blood samples. RESULTS: During the treatment, serum oestradiol and progesterone concentrations increased significantly. In the oestradiol cycles, leptin concentrations were not affected by treatment and did not differ from those in controls. In the oestradiol+progesterone cycles, leptin concentrations (mean +/- SEM) increased in all women from cycle day 3 (8.6 +/- 1.1 ng/ml) to days 5 (12.2 +/- 1.8 ng/ml, P < 0.01) and 6 (11.9 +/- 2.0, P < 0.05), and were at these points significantly higher than in the control cycles (P < 0.05). The mean percentage increase from day 3 to the peak concentration on days 5 or 6 was 62.6 +/- 6.8%. Leptin concentrations returned to the pretreatment value on day 7, together with the concentrations of oestradiol and progesterone. In the oestradiol+progesterone cycles, leptin concentrations correlated significantly with oestradiol and progesterone concentrations, but not with FSH and LH concentrations. CONCLUSIONS: These results show, for the first time, that leptin secretion can be stimulated in women by the administration of oestradiol plus progesterone. This may explain the increased concentrations of leptin during the luteal phase of the normal menstrual cycle.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11527883&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone receptor isoform A inhibits isoform B-mediated transactivation in human amnion.

Pieber D, Allport VC, Bennett PR.

Institute of Obstetrics and Gynecology, Imperial College School of Medicine, Queen Charlotte's and Chelsea Hospital, London, UK. doris.pieber uni-graz.ac.at

Human amnion cells were transfected with progesterone receptor A and/or B, and the progesterone-dependent reporter construct, mouse mammary tumor virus promoter (MMTV), linked to a luciferase gene. In progesterone receptor B-expressing amnion that had been cultured before the onset of labour, treatment with progesterone resulted in an eightfold increase of the reporter activity, whereas in laboured cells, no such increase was seen. In contrast, progesterone receptor A was a weak activator of transcription in laboured and non-laboured amniocytes. When the isoforms A and B of the progesterone receptor were co-transfected, progesterone receptor A exhibited a marked inhibitory effect on progesterone receptor B-mediated transcription. These results show that progesterone receptors A and B function differentially, and progesterone receptor A is a transdominant repressor of progesterone receptor B-mediated transcription in human term amnion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11553358&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone accelerates the onset of capacitation in mouse sperm via T-type calcium channels.

Senuma M, Yamano S, Nakagawa K, Irahara M, Kamada M, Aono T.

Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima, Japan.

This study was undertaken to evaluate whether progesterone induces capacitation of mouse spermatozoa. When sperm were evaluated by chlortetracycline staining, addition of progesterone significantly increased the proportion of spermatozoa exhibiting the B pattern at 60 minutes of incubation, compared with that before incubation (23 +/- 6.2% vs. 13 +/- 2.9%, p < 0.01) and that in hTF medium without progesterone (23 +/- 6.2% vs. 13 +/- 4.2%, p < 0.01). If the redistribution of proteins in sperm plasma membrane such as protein binding calcium ion were defined as capacitation, it could be said that progesterone promoted capacitation of mouse sperm. This progesterone-induced capacitation was prevented by depletion of extracellular calcium ion and addition of NiCl2, a T-type calcium channel blocker, although thapsigargin, an inhibitor of Ca2+-ATPase, did not increase the number of capacitated sperm (B pattern; progesterone vs. progesterone + depletion of calcium ion, 18 +/- 3.5% vs. 8 +/- 2.5%, p < 0.05, progesterone vs. progesterone + NiCl2, 20 +/- 3.8% vs. 6 +/- 5.2%, p < 01). Furthermore, genistein, a protein tyrosine phosphorylation inhibitor, inhibited progesterone-induced capacitation (B pattern; progesterone vs. progesterone + genistein, 20 +/- 3.8% vs. 11 +/- 2.4%, p < 01). In conclusion, progesterone induces capacitation in mouse sperm and this capacitation may be associated with calcium influx and tyrosine phosphorylation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11554684&dopt=Abstract progesterone, progesterone cream



progesterone cream
Effect of progesterone on the invasive properties and tumor growth of progesterone receptor-transfected breast cancer cells MDA-MB-231.

Lin VC, Eng AS, Hen NE, Ng EH, Chowdhury SH.

Department of Clinical Research, Singapore General Hospital, Singapore, Republic of Singapore, 169608. gcrlcl sgh.gov.sg

One of the potential therapeutic interventions to hormone-independent breast cancer would be to reactivate the expression of estrogen receptor or progesterone receptor (PR) in the tumor cells so as to render the tumor responsive to the hormones. We have reported previously that progesterone markedly inhibited cell growth and induced remarkable focal adhesions in PR-transfected MDA-MB-231 cells. The aim of this study was to determine the effects of progesterone on the invasive properties and in vivo tumor growth of PR-transfected MDA-MB-231 cells. It was found that progesterone has increased cell resistance to trypsin digestion and increased cell attachment to extracellular matrix proteins, especially laminin and fibronectin. In vitro invasion assays using modified Boyden chambers showed that progesterone increased cell migration through matrix protein-coated membranes. However, Northern blotting analysis demonstrated that progesterone strongly down-regulated (up to 60-fold) the gene expression of urokinase plasminogen activator and increased (up to 5-fold) the expression of tissue-type plasminogen activator in these cells. This pattern of gene regulation suggested an inhibition of cell invasiveness because numerous clinical studies have indicated that low levels of urokinase plasminogen activator and high levels of tissue-type plasminogen activator in breast cancer are associated with favorable prognosis. Furthermore, animal studies showed that progesterone strongly inhibited the tumor formation and growth in Scid mice. After 12 weeks of inoculation, the median weight of tumors in the progesterone-treated group was 25 mg compared with 203 mg in the placebo group (P < 0.001). These results suggest that progesterone may provide effective treatment for estrogen receptor- and PR-negative breast cancer if the PR expression were reactivated. Alternatively, activation of progesterone-mediated molecular pathways in hormone-independent breast cancer may achieve similar therapeutic effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11555606&dopt=Abstract progesterone, progesterone cream