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In vitro progesterone production by maternal and embryonic tissues during gestation in the southern snow skink (Niveoscincus microlepidotus).

Girling JE, Jones SM.

School of Zoology, University of Tasmania, Box 252-05, 7001, Hobart, Tasmania, Australia. jane.girling med.monash.edu.au

The southern snow skink, Niveoscincus microlepidotus, has a protracted gestation, lasting approximately one year. Ovulation occurs in spring (November) and embryonic development is completed by early autumn (March); however, birth does not occur until the following spring. Previous studies have shown that plasma progesterone concentration peaks in preovulatory females (spring, October), remains high during early gestation, and decreases to basal by autumn. In vitro progesterone production by corpora lutea, non-luteal ovary, anterior oviduct, placental tissues, muscle, and embryonic adrenal-gonads from N. microlepidotus was assessed throughout gestation. Tissues were incubated with or without the precursor pregnenolone for 3h at 24 degrees C; the resulting media were analysed for progesterone using radioimmunoassay. In vitro progesterone production by corpora lutea in media only was high during early gestation, dropping to basal by autumn. Maternal adrenal glands produced progesterone in vitro in media only throughout gestation; however, the pattern of production did not correlate with plasma concentrations and may represent steroid that is normally converted to corticosterone. Non-luteal ovary, anterior oviduct, placental tissues, muscle, and embryonic adrenal-gonads produced minimal progesterone in media only, but were able to convert pregnenolone to progesterone; this suggests steroid metabolic capability within these tissues. Further research is needed to address the possible endocrine role(s) of placental and embryonic tissues during gestation in viviparous squamates.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12899851&dopt=Abstract progesterone, progesterone cream



progesterone cream
Anti-glucocorticoid effects of progesterone in vivo on rat adipose tissue metabolism.

Pedersen SB, Kristensen K, Richelsen B.

Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus University Hospital, DK-8000 Aarhus C., Denmark. amtssp aau.dk

Steroid hormones seem to be important for adipose tissue metabolism and accumulation. As progesterone has been suggested to modulate the glucocorticoid effects, the interactions between glucocortioid and progesterone on adipose tissue metabolism were investigated.Forty-eight male Wistar rats were adrenectomized and divided into four groups; controls (treated with vehicle only), dexamethasone treated (10 micro g per rat), progesterone treated (5mg per rat) and the last group received both dexamethasone and progesterone.The dexamethasone-treated group had a significant loss of body weight and smaller intra-abdominal fat depots compared to the control group in addition, dexamethasone increased LPL-activity and increased catecholamine stimulated lipolysis. When progesterone was given concomitantly the dexamethasone effects on adipose tissue mass, LPL-activity and lipolysis were blocked. When given alone progesterone had no influence on body weight, amount of adipose tissue, lipolysis or LPL-activity.These data indicate that progesterone acts as an anti-glucocorticoid in adipose tissue in vivo, thus attenuating the glucocorticoid effect on adipose tissue metabolism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12906939&dopt=Abstract progesterone, progesterone cream



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Passage of progesterone into the brain changes with photoperiod in the ewe.

Thiery JC, Robel P, Canepa S, Delaleu B, Gayrard V, Picard-Hagen N, Malpaux B.

UMR 6073 INRA-CNRS-Universite de Tours, Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France. thiery tours.inra.fr

In this study we tested the hypothesis that photoperiod can modulate steroid access to the brain in a seasonal breeder. To this goal, we compared the passage of exogenous progesterone to the brain of female sheep maintained under short (SD) or long (LD) daylengths. In the first experiment, we studied two groups of ovariectomized females maintained under SD or LD, for three artificial cycles, consisting of bearing a subcutaneous oestradiol implant (E2-treated) and an intravaginal device releasing progesterone (CIDR). During the third cycle, the concentrations of progesterone and of its metabolites 5alpha-dihydroprogesterone and 3alpha-hydroxy-5alpha-pregnan-20-one were measured in the preoptic area (POA). The levels of progesterone in the POA were higher in ewes under LD than under SD while the amounts of metabolites were unchanged. In the second experiment, we compared ovariectomized female sheep equipped with a cannula in the third ventricle to sample the cerebrospinal fluid (CSF) under LD vs. SD. After progesterone (1 mg and 10 mg) was injected into the carotid artery, it was only detectable in the cerebrospinal fluid in sheep under LD. In the third experiment, we compared progesterone concentration in plasma and CSF in two groups of SD vs. LD ovariectomized E2-treated ewes for 2 h under CIDR treatment. Despite similar progesterone plasma concentrations, concentration in the CSF was 2.5 times higher in SD than in LD. Our results suggest a physiological modulation of the passage of progesterone to the brain according to the photoperiod.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12925015&dopt=Abstract progesterone, progesterone cream



progesterone cream
Pitfalls in assessment of progesterone production by granulosa cells cultured in contact with silicone rubber or paraffin oil.

Reinsberg J, Ackermann D, van der Ven H.

Department of Gynecological Endocrinology and Reproductive Medicine, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. Jochen.Reinsberg ukb.uni-bonn.de

BACKGROUND: The influence of silicone templates, used for compartmentalization of culture dishes, on progesterone accumulation in granulosa cell cultures is studied and compared with the effect of paraffin oil, which is frequently used to cover oocyte/embryo cultures. METHODS: Human granulosa-lutein cells were cultured in culture dishes compartmentalized by silicone templates, or in polystyrene plates under paraffin oil. Progesterone concentrations in the culture supernatant were compared with controls cultured in polystyrene plates. RESULTS: The progesterone concentration in culture supernatant was grossly reduced in silicone template cultures (2+/-0.7% of control). No inhibitory activity was identified in medium conditioned by preincubation with silicone rubber, but progesterone was absorbed from spiked medium incubated in silicone templates (recovery <2%). Progesterone concentration in culture supernatant was also reduced by a paraffin oil overlay (38+/-3% of control). From steroid spiked microdrops under oil, <2% of progesterone and 85+/-4% of estradiol was recovered. CONCLUSION: The steroidogenesis of cells cultured in silicone templates or under oil cannot be assessed correctly. It has to be considered that the concentration of lipophilic compounds may be grossly changed due to absorption by silicone rubber or paraffin oil.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12928937&dopt=Abstract progesterone, progesterone cream



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Estradiol and progesterone can prevent rat mammary cancer when administered concomitantly with carcinogen but do not modify surviving tumor histology, estrogen receptor alpha status or Ha-ras mutation frequency.

Swanson SM, Christov K.

Department of Medicinal Chemistry & Pharmacognosy, Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612-7231, USA. swanson uic.edu

An early full-term pregnancy is protective against mammary cancer in both humans and rodents. Treating rats with two hormones of pregnancy, estradiol and progesterone, for 5 weeks renders the rat mammary glands refractory to carcinogenesis. Our objectives was to determine if a shortened regimen (3 weeks) would be as effective as the 5-week regimen and to determine if the mammary gland was vulnerable to carcinogenic insult during the hormone treatments. We also examined cancers that survived the chemopreventive regimen to see if those tumors were particularly aggressive compared to control tumors (i.e., less differentiated, estrogen receptor alpha (ER alpha)-negative or harbored mutations in Ha-ras). In the first experiment, Lewis rats were injected with N-methyl-N-nitrosourea (MNU, 50 mg/kg) at 50 days of age. At 60 days of age, the rats were either mated and allowed to nurse their young for 3 weeks, treated with hormone vehicle for 5 weeks, or 17 beta-estradiol (E, 20 micrograms) and progesterone (P, 4 mg) 5 times per week for 3 or 5 weeks. All the rats exposed to MNU but not estradiol and progesterone developed multiple mammary cancers. Pregnancy reduced multiplicity to 0.40 cancers/rat. Treatments of estradiol and progesterone for 3 or 5 weeks reduced cancer multiplicity and increased latency to a similar degree as pregnancy. Mammary cancers from each group displayed a similar spectra of histologic class, estrogen receptor alpha (ER alpha) content and Ha-ras mutation status. In the second experiment, 50-day-old rats were treated for five weeks with either estradiol and progesterone or vehicle as above beginning at 60 days of age and treated with MNU at 50, 64, 78 or 92 days of age. In each case, estradiol and progesterone treatments resulted in significantly reduced mammary tumor frequency. These results demonstrate that a three-week regimen of estradiol and progesterone can protect the mammary gland from chemically-induced carcinogenesis even when carcinogen exposure occurs concomitant with estradiol and progesterone stimulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12931682&dopt=Abstract progesterone, progesterone cream



progesterone cream
Acute reduction in serum progesterone concentrations after feed intake in dairy cows.

Vasconcelos JL, Sangsritavong S, Tsai SJ, Wiltbank MC.

Department of Dairy Science, University of Wisconsin, Madison, WI 53706, USA.

This study tested the hypothesis that high feed consumption will acutely decrease circulating progesterone concentrations. In the first experiment, a Latin Square design was used to test whether feeding pattern would alter circulating progesterone in pregnant lactating Holstein cows (n = 12). Feed was removed for 12h before the experiment and cows were then either fed 100% of the total mixed ration (TMR), 50% of TMR every 12h, 25% of TMR every 6h, or left unfed for an additional 12h. Blood samples were taken every hour for 24h. Provision of 100 or 50% of TMR decreased circulating progesterone by 1h after feeding and progesterone remained depressed until 8-9h after feeding. Feeding 25% of TMR did not reduce circulating progesterone concentrations. Experiment 2 used a crossover design to measure the effect of acute feeding on circulating progesterone and LH concentrations during delivery of a constant amount of exogenous progesterone (Eazi-Breed CIDRs) in lactating Holstein cows (n = 8) and nonpregnant dry Holstein cows (n = 6). Blood samples were taken every 15min for 8h. There was no change in serum progesterone during the 8h treatment period in unfed cows; however, feeding decreased (P<0.05) circulating progesterone between 2 and 6h after feeding. In lactating cows, feeding increased mean LH (P<0.05). There were more LH pulses (P = 0.01) in lactating than nonlactating cows. Thus, acute feeding reduced circulating progesterone in pregnant lactating cows apparently due to an increase in progesterone metabolism. Interestingly, feeding multiple smaller meals eliminated the acute effect of feeding on circulating progesterone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12935858&dopt=Abstract progesterone, progesterone cream



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[Receptivity to the sex steroids, physiopathological aspects]

[Article in French]

Bercovici JP.

PIP: The steroid hormones are recognized and fixed by special cytoplasmic proteins in the target tissue called receptors. Most circulating natural steroids are tied to transport proteins. Estradiol and progesterone are active as such in the receptor cells, but testosterone is transformed into dihydrotestosterone in situ under the influence of the enzyme 5 alpha reductase before combining with the receptor. Receptivity may be exacerbated or reduced. Exacerbation is particularly likely when physiological control mechanisms are deficient. Testosterone has a biological effect at the level of the Wolfian apparatus in the embryo and in the muscle and bone of the adult. The activity of perineal 5 alpha reductase implicated in these phenomena and the hepatic 5 alpha reductase activity implicated in the degradation of testosterone are found in both sexes and are under genetic influence independent of the male hormone. Problems in receptivity to the male hormone are well known to clinicians. Hirsutism, whatever its cause, is always associated with great cutaneous 5 alpha reductase activity. The use of antiandrogens derived from synthetic progestagens has transformed treatment of hirsutism. Male pseudohermaphrodism may be secondary to an insufficient testosterone production or to primary resistence to the male hormone, in which case the plasma concentration of testosterone is always greater than normal. The characteristic case is of a deficit of 5 alpha reductase and feminization of the testicle. 5 alpha reductase deficiency causes sexual ambiguity at birth. Absence of the testosterone receptor at both the perineal and public levels explains why attempts to treat these disorders with high doses of testosterone or dihydrotestosterone always fail. Problems in receptivity to the male hormone have been found to cause other pathologies, such as severe oligospermia. The quantity of estradiol and progesterone receptors varies according to the volume of circulating estradiol and of progesterone. Progesterone is a natural antiestrogen; it limits the activity of estradiol by favoring the transformation of estradiol into estrone and decreases the synthesis of estradiol receptors. The normal endometrium may become hyperplasic after menopause, the 1st stage in development of endometrial cancer. Continuous estrogen stimulation not countebalanced by progesterone permits the transformation. Study of estradiol and progesterone receptors in mammary fibroadenomas has shown that estradiol receptors increase to a maximum in the preovulatory period and diminish in the luteal phase. The increase in estradiol is followed by an increase in progesterone receptors. Since 1971 it has been apparent that breast cancer susceptible to improvement by hormonal treatment were rich in estrogen receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12313177&dopt=Abstract progesterone, progesterone cream