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Two methods of inducing low plasma progesterone concentrations have different effects on dominant follicles in cows.

Shaham-Albalancy A, Rosenberg M, Folman Y, Graber Y, Meidan R, Wolfenson D.

Department of Animal Science, Faculty of Agriculture, The Hebrew University, Rehovot, Israel.

The effects of two methods of inducing low progesterone concentrations on the shape of the plasma progesterone curve and on follicular characteristics in lactating cows were studied. A low ascending progesterone curve was elicited by three PGF2alpha injections on d 3 to 4 of the estrous cycle; a low constant curve by induction of corpus luteum regression on d 6 and insertion of two progesterone-containing intravaginal devices from d 6 to 15 of the cycle. Plasma progesterone concentration was highest in the untreated control group, intermediate in low ascending group, and lowest in the low constant group. On d 15, both control and low ascending groups had one large healthy and one large atretic follicle, suggesting a turnover of follicular waves; in the low constant group, the presence of only one very large healthy follicle indicated follicular persistence. Estradiol concentration in the follicular fluid and its production by granulosa cells were highest in the low constant, intermediate in the low ascending, and lowest in the control group. Androstenedione concentration in the follicular fluid and its production by theca cells were higher in the low constant than in the low ascending and control groups. The results indicate that the low ascending progesterone curve affected follicular development and steroidogenesis differently from the low constant curve. We suggest that the low ascending curve mimics the effects of naturally occurring low plasma progesterone concentrations better, and it might, therefore, be used as a model for studying the effects of low plasma progesterone on fertility.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11132845&dopt=Abstract progesterone, progesterone cream



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Feed restriction and insulin treatment affect subsequent luteal function in the immediate postovulatory period in pigs: progesterone production in vitro and messenger ribonucleic acid expression for key steroidogenic enzymes.

Mao J, Treacy BK, Almeida FR, Novak S, Dixon WT, Foxcroft GR.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5.

Progesterone production and release in vitro, and mRNA expression for key steroidogenic enzymes, were studied in luteal tissue recovered in the immediate postovulatory period from cyclic gilts allocated to one of three treatments: moderate feed restriction during the first (RH) or second week of the estrous cycle, with (HR+I) or without (HR) concomitant injections of long-acting insulin. Time of feed restriction affected neither progesterone production or release, nor mRNA expression for several key steroidogenic enzymes. However, luteal tissue from RH but not from HR gilts responded to LH stimulation by increasing progesterone production and release (P: < 0.05). Insulin treatment increased progesterone production and release, restored luteal tissue responsiveness to LH, up-regulated steroidogenic enzyme mRNA expression, and down-regulated the tissue inhibitor of metalloproteinase-I mRNA expression in HR+I compared with HR gilts (P: < 0.05). In vitro progesterone production and gene expression were affected by time of tissue collection after ovulation in RH and HR gilts but not in HR+I gilts, and were correlated with temporal changes in oviductal and peripheral plasma progesterone concentrations. Inherent differences in luteal function therefore appear to mediate latent effects of nutrition and insulin treatment on circulating progesterone concentrations in the critical postovulatory period in gilts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11133694&dopt=Abstract progesterone, progesterone cream



progesterone cream
Molecular species analysis of 1,2-diacylglycerol released in response to progesterone binding to the amphibian oocyte plasma membrane.

Morrill GA, Ma G, Kostellow A.

Department of Physiology and Biophysics, Albert Einstein College of Medicine, 10461, Bronx, NY, USA. morrill aecom.yu.edu

Progesterone, the physiological inducer of amphibian meiosis, acts within minutes at plasma membrane receptors of the Rana pipiens oocyte to release 1,2-diacylglycerol (DAG) from plasma and intracellular membranes. High-performance liquid chromatography (HPLC) analysis of lipid extracts of uninduced oocytes indicates the presence of at least three classes of DAG with a total DAG content of about 150 micromol/kg wet weight. Within 3-5 min after exposure to progesterone, there was a differential increase in all three DAG classes with a twofold increase in total DAG by 10 min. The fatty acid composition of the DAGs in uninduced and progesterone-stimulated oocytes was compared using thin layer chromatographic analysis of lipid extracts from oocytes double-labeled with [14C] or [3H]glycerol and [14C] or [3H]fatty acids. The ratio of labeled fatty acid/labeled glycerol was measured in phosphatidylcholine (PC), phosphatidylinositol (PI) and DAG. The linoleic (18:2) or arachidonic (20:4) acid/glycerol ratios in basal DAG were low compared to that in PC or PI. In contrast, the myristic (14:0), palmitic (16:0) or oleic (18:1) acid/glycerol ratios in basal DAG were relatively high compared to the ratio in PC and PI. A transient increase in both linoleic and palmitic acid labeling of DAG occurred within the first 1-2 min in progesterone-treated oocytes, followed by a return to or below the basal level. Arachidonic and myristic acid labeling of DAG fall within the first minute after progesterone treatment, followed by a sustained rise over the next 10 min. The [3H]oleic acid/[14C]glycerol ratio of DAG does not change significantly following exposure to progesterone. Pretreatment with a phospholipid N-methylation inhibitor (2-methylaminoethane) precluded the rise in linoleic and palmitic acid-rich DAG, whereas pretreatment with a diglyceride kinase inhibitor (D102) produced a sustained elevation of linoleic and palmitic acid-rich DAG. These results indicate that the DAG released in response to progesterone is composed of multiple new molecular species of DAG and that both the palmitate and linolate-rich forms are rapidly phosphorylated to form phosphatidic acid (PA). The newly formed DAG species differ from the basal DAG species and reflect sequential activation of sphingomyelin (SM) synthase, PC-specific phospholipase D (PLD) and PI-specific phospholipase C in response to progesterone, which we have described previously.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11152965&dopt=Abstract progesterone, progesterone cream



progesterone cream
The rate-determining step in P450 C21-catalyzing reactions in a membrane-reconstituted system.

Kominami S, Owaki A, Iwanaga T, Tagashira-Ikushiro H, Yamazaki T.

Faculty of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashihiroshima 739-8521, Japan. kominam hiroshima-u.ac.jp

Adrenal cytochrome P450 C21 in a membrane-reconstituted system catalyzed 21-hydroxylation of 17alpha-hydroxyprogesterone at a rate higher than that for progesterone in the steady state at 37 degrees C. The rate of product formation in the steady state increased with the concentration of the complex between P450 C21 and the reductase in the membranes. The complex formation was independent of the volume of the reaction, showing that the effective concentrations of the membrane proteins should be defined with the volume of the lipid phase. The rates of conversion of progesterone and 17alpha-hydroxyprogesterone to the product in a single cycle of the P450 C21 reaction were measured with a reaction rapid quenching device. The first-order rate constant for the conversion of progesterone by P450 C21 was 4.3 +/- 0.7 s(-)1, and that for 17alpha-hydroxyprogesterone was 1.8 +/- 0.5 s(-)1 at 37 degrees C. It was found from the analysis of kinetic data that the rate-determining step in 21-hydroxylation of progesterone in the steady state was the dissociation of product from P450 C21, whereas the conversion to deoxycortisol was the rate-determining step in the reaction of 17alpha-hydroxyprogesterone. The difference in the rate-determining steps in the reactions for the two substrates was clearly demonstrated in the pre-steady-state kinetics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11154687&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells.

Otsuki M, Saito H, Xu X, Sumitani S, Kouhara H, Kishimoto T, Kasayama S.

Department of Molecular Medicine, Osaka University Graduate School Medicine, Suita-City, Osaka, Japan.

-It has been shown that ovarian steroid hormones can reduce the incidence of cardiovascular disease in postmenopausal women. As hormone replacement therapy for postmenopausal women, progestins are added to estrogens to eliminate the increased risk of endometrial cancer. However, the effects of progestins on the atherogenic process have not been well understood. In the present study, we examined the effects of progestins on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Immunocytochemical analysis revealed the presence of progesterone receptors in HUVECs. Progesterone clearly inhibited tumor necrosis factor-alpha-activated expression of VCAM-1 protein and its mRNA in HUVECs. Synthetic progesterone receptor agonist R5020 also inhibited the tumor necrosis factor-alpha-activated VCAM-1 expression, whereas medroxyprogesterone acetate (MPA) failed to do so. Electrophoretic mobility shift assays demonstrated that progesterone, but not MPA, inhibited DNA binding of the transcription nuclear factor-kappaB, which is critical for the inducible expression of VCAM-1. Because the expression of VCAM-1 is one of the earliest events that occurs in the atherogenic process, this adhesion molecule might be a target molecule for progesterone on vascular walls. The contrasting effects of progesterone and MPA seem clinically important, inasmuch as MPA is a widely used progestin in the regimen of hormone replacement therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11156860&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone receptor and dopamine receptors are required in Delta 9-tetrahydrocannabinol modulation of sexual receptivity in female rats.

Mani SK, Mitchell A, O'Malley BW.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Ovarian steroids, estrogen and progesterone, influence the sensitivity of certain neural processes to cannabinoid treatment by modulation of brain dopaminergic activity. We examined the effects of the active ingredient of cannabis, Delta(9)-tetrahydrocannabinol (THC), on sexual behavior in female rats and its influence on steroid hormone receptors and neurotransmitters in the facilitation of sexual receptivity. Our results revealed that the facilitatory effect of THC was inhibited by antagonists to both progesterone and dopamine D(1) receptors. To test further the idea that progesterone receptors (PR) and/or dopamine receptors (D(1)R) in the hypothalamus are required for THC-facilitated sexual behavior in rodents, antisense and sense oligonucleotides to PR and D(1)R were administered intracerebroventricularly (ICV) into the third cerebral ventricle of ovariectomized, estradiol benzoate-primed rats. Progesterone- and THC-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides to PR or to D(1)R. Antagonists to cannabinoid receptor-1 subtype (CB(1)), but not to cannabinoid receptor-2 subtype (CB(2)) inhibited progesterone- and dopamine-facilitated sexual receptivity in female rats. Our studies indicate that THC acts on the CB(1) cannabinoid receptor to initiate a signal transduction response that requires both membrane dopamine and intracellular progesterone receptors for effective induction of sexual behavior.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11158625&dopt=Abstract progesterone, progesterone cream



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Unmasking the progesterone receptor in the preoptic area and hypothalamus of the ewe: no colocalization with gonadotropin-releasing neurons.

Skinner DC, Caraty A, Allingham R.

Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, BS40 5DU, United Kingdom. donal.c.skinner bristol.ac.uk

Progesterone powerfully inhibits GnRH secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Visualization of the neural ovine progesterone receptor has proved elusive but, using a high temperature antigen unmasking technique, the progesterone receptor was revealed in the ewe brain. Progesterone receptors were located in the preoptic-hypothalamic continuum, especially in the preoptic area, ventrolateral region of the ventromedial nucleus and the arcuate nucleus. This study also suggests that the inhibitory action of progesterone on GnRH release is not transduced directly through the GnRH neurons as a single GnRH perikaryon of 732 was immunoreactive for the progesterone receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11159827&dopt=Abstract progesterone, progesterone cream