progesterone cream
Ultrasonography and hormone profiles of persistent ovarian follicles (cysts) induced with low doses of progesterone in cattle.

Noble KM, Tebble JE, Harvey D, Dobson H.

Department of Clinical Veterinary Science and Animal Husbandry, University of Liverpool, Leahurst, Chester High Road, Neston CH64 7TE, UK.

The aims of this study were to expose dominant ovarian follicles at the end of the oestrous cycle to low progesterone concentrations similar to those that occur during stress, and to examine the effect of a subsequent small increase in progesterone 10 days later. Half a progesterone releasing intravaginal device (0.5 PRID) was administered to 13 heifers from day 15 of the oestrous cycle. In group 1 (n = 7), one 0.5 PRID remained in place until day 40 or until each heifer ovulated. In group 2 (n = 6), the first 0.5 PRID was removed on day 28, and replaced immediately with a second 0.5 PRID. Ultra-sonography and blood collection (10 ml) were conducted each day for 26 days from day 14 and then on alternate days. The largest follicle that emerged during the first 5 days after insertion of the initial 0.5 PRID remained > 10 mm in diameter for 15.3 +/- 1.7 and 11.6 +/- 0.4 days in groups 1 and 2, respectively. This period of dominance, during which no other follicles emerged, was closely correlated with the duration of plasma oestradiol concentrations exceeding 10 pg ml(-1). In four heifers from group 1, the persistent follicle ovulated between days 30 and 37 (sub-group 1a; 0.5 PRID expelled). In three heifers from sub-group 1b (0.5 PRID retained), the dominant follicle secreted oestradiol for 17 +/- 5 days but remained detectable by ultrasonography for a total of 33 +/- 8 days (range 26-52 days). Monitoring continued beyond day 40 in these animals. In group 2, the new 0.5 PRID inserted on day 28 resulted in an increase in plasma progesterone concentration of 0.9 +/- 0.3 ng ml(-1). Simultaneously, oestradiol decreased by 10.1 +/- 3.3 pg ml(-1), and a new follicular wave emerged 5-7 days later. In conclusion, exposure to very low concentrations of progesterone produced persistent follicles that secreted oestradiol for 17 days. This oestradiol production could be disrupted by a second increase of 0.9 ng ml(-1) in peripheral progesterone concentration. In the absence of the second progesterone treatment, some of the persistent follicles remained detectable by ultrasonography for up to 52 days, despite cessation of oestradiol secretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11058451&dopt=Abstract progesterone, progesterone cream



progesterone cream
Effect of progesterone on the activation of neurones of the supraoptic nucleus during parturition.

Antonijevic IA, Russell JA, Bicknell RJ, Leng G, Douglas AJ.

Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.

Parturition is driven by a pulsatile pattern of oxytocin secretion, resulting from burst firing activity of supraoptic oxytocin neurones and reflected by induction of Fos expression. Rats were injected with progesterone on day 20 of pregnancy to investigate the role of the decreasing progesterone:ratio oestrogen ratio, which precedes delivery, in the activation of supraoptic neurones. Progesterone delayed the onset of birth by 28 h compared with vehicle (control) and prolonged the duration of delivery, which was overcome by pulsatile injections of oxytocin, indicating that the slow delivery may reflect impaired oxytocin secretion. Parturient rats pretreated with progesterone had fewer Fos immunoreactive nuclei in the supraoptic nucleus than did parturient rats pretreated with vehicle. The number of Fos immunoreactive nuclei was not restored after oxytocin injection, indicating that appropriate activation of oxytocin neurones is impaired by progesterone and also that there is a lack of stimulatory afferent drive. Fos expression increased in the nucleus of the tractus solitarius during parturition in rats pretreated with either vehicle or progesterone, but not in rats that had been pretreated with progesterone and induced with oxytocin, indicating that this input was inhibited. Endogenous opioids inhibit oxytocin neurones in late pregnancy and the opioid antagonist, naloxone, increases Fos expression in supraoptic nuclei by preventing inhibition. However, progesterone attenuated naloxone-induced Fos expression in the supraoptic nucleus in late pregnancy and naloxone administered during parturition did not accelerate the duration of births delayed by progesterone administration, indicating that progesterone does not act by hyperactivation of endogenous opioid tone. RU486, a progesterone receptor antagonist, enhanced supraoptic neurone Fos expression in late pregnancy, indicating progesterone receptor-mediated actions. Thus, progesterone withdrawal is necessary for appropriate activation of supraoptic and tractus solitarius neurones during parturition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11058452&dopt=Abstract progesterone, progesterone cream



progesterone cream
Increased progesterone secretion and 3 beta-hydroxysteroid dehydrogenase activity in human cumulus cells by pregnenolone is limited to the high steroidogenic active cumuli.

Bar-Ami S, Gitay-Goren H.

Department of Obstetrics and Gynecology, Rambam Medical Centre, Haifa, Israel. sgyss zahav.net.il

PURPOSE: Several reports imply that lower progesterone secretion by cumulus-oocyte complexes (COCs) is associated with lower fertilization in the corresponding oocyte. The possible role of progesterone in oocyte fertilization in humans was studied using two approaches: (a) increasing the total progesterone secretion by culturing more than one COC per dish; and (b) increasing the cumulus cell progesterone secretion by providing pregnenolone as a substrate. METHODS: Mature COCs were cultured individually or cocultured in groups. Oocyte fertilization and progesterone secretion were tested after 20 hr and 3 days in culture, respectively. The cumuli from individually plated COCs were cultured in the absence of oocyte for an additional 3 days in order to test the effects of pregnenolone on progesterone secretion and the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity. A comparable study with pregnenolone was performed on the corresponding granulosa-lutein cells. RESULTS: Increasing the number of COC to two instead of one led to a significant increase in both fertilization rate and progesterone secretion. The addition of pregnenolone during days 3-6 increased significantly both progesterone secretion and 3 beta-HSD activity. Comparable results were observed in granulosa-lutein cells subjected to pregnenolone treatment. Following the first 3 days culture, cumulus masses were categorized as secreting high or low progesterone levels. Adding pregnenolone had a greater effect on both progesterone secretion and 3 beta-HSD activity in the high-progesterone-secreting cumuli. CONCLUSIONS: Addition of pregnenolone increased progesterone secretion and 3 beta-HSD more efficiently in the higher-progesterone-secreting cumuli. Coculture of two COCs instead of one led to a higher fertilization rate and greater progesterone secretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11062854&dopt=Abstract progesterone, progesterone cream



progesterone cream
Progesterone and testosterone modulate the convulsant actions of pentylenetetrazol and strychnine in mice.

Pesce ME, Acevedo X, Bustamante D, Miranda HE, Pinardi G.

Faculty of Medical Sciences, Pharmacology Program, University of Santiago de Chile.

The influence of progesterone and testosterone on the incidence of seizures after administration of intraperitoneal pentylenetetrazol and subcutaneous strychnine was evaluated in mice. Pentylenetetrazol and strychnine were administered in doses that induced seizures in 40-50% of control mice in dioestrus (48 and 0.9 mg/kg, respectively). The percentage of seizures induced by pentylenetetrazol and strychnine was significantly lower in female mice in prooestrus/oestrus, when progesterone levels are high, than in dioestrus, when progesterone levels are low. Pretreatment of pentylenetetrazol-challenged mice with progesterone (250 microg/kg) increased the incidence of seizures in prooestrus/oestrus, without affecting seizures in dioestrus. The same pretreatment in strychnine-challenged mice also increased the incidence of seizures in prooestrus-dioestrus, but significantly reduced the incidence of seizures in dioestrus. In addition, progesterone pretreatment significantly increased the percentage of deaths induced by strychnine in prooestrus-oestrus, reducing deaths in dioestrus. Orchidectomized male mice had a significantly higher incidence of seizures after administration of pentylenetetrazol and strychnine than control mice. Administration of 11 daily doses of 250 microg/kg of testosterone to castrated mice significantly reduced the incidence of seizures induced by pentylenetetrazol. These results confirm the modulatory influence of reproductive steroids on the excitability of the central nervous system and the possible clinical importance of progesterone and testosterone in the management of partial epilepsy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11068851&dopt=Abstract progesterone, progesterone cream



progesterone cream
A rational approach to Re-engineer cytochrome P450 2B1 regioselectivity based on the crystal structure of cytochrome P450 2C5.

Kumar S, Scott EE, Liu H, Halpert JR.

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555-1031, USA. sakumar utmb.edu

The regioselectivity for progesterone hydroxylation by cytochrome P450 2B1 was re-engineered based on the x-ray crystal structure of cytochrome P450 2C5. 2B1 is a high K(m) progesterone 16alpha-hydroxylase, whereas 2C5 is a low K(m) progesterone 21-hydroxylase. Initially, nine individual 2B1 active-site residues were changed to the corresponding 2C5 residues, and the mutants were purified from an Escherichia coli expression system and assayed for progesterone hydroxylation. At 150 microm progesterone, I114A, F297G, and V363L showed 5-15% of the 21-hydroxylase activity of 2C5, whereas F206V showed high activity for an unknown product and a 13-fold decrease in K(m). Therefore, a quadruple mutant, I114A/F206V/F297G/V363L (Q), was constructed that showed 60% of 2C5 progesterone 21-hydroxylase activity and 57% regioselectivity. Based on their 2C5-like testosterone hydroxylation profiles, S294D and I477F alone and in combination were added to the quadruple mutant. All three mutants showed enhanced regioselectivity (70%) for progesterone 21-hydroxylation, whereas only Q/I477F had a higher k(cat). Finally, the remaining three single mutants, V103I, V367L, and G478V, were added to Q/I477F and Q/S294D/I477F, yielding seven additional multiple mutants. Among these, Q/V103I/S294D/I477F showed the highest k(cat) (3-fold higher than that of 2C5) and 80% regioselectivity for progesterone 21-hydroxylation. Docking of progesterone into a three-dimensional model of this mutant indicated that 21-hydroxylation is favored. In conclusion, a systematic approach to convert P450 regioselectivity across subfamilies suggests that active-site residues are mainly responsible for regioselectivity differences between 2B1 and 2C5 and validates the reliability of 2B1 models based on the crystal structure of 2C5.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12609983&dopt=Abstract progesterone, progesterone cream



progesterone cream
[Changes in preovulatory molecular relationship between estradiol and progesterone in patients undergoing controlled ovarian hyperstimulation. Can they be used for the evaluation of ovarian reserve?]

[Article in Spanish]

Kably Ambe A, Barron Vallejo J, Fernandez Castro M, Karchmer Krivitzky S.

Centro Especializado para la Atencion de la Muje, Hospital Angeles de las Lomas.

The objective was to evaluate if the preovulatory molecular ratio between progesterone and estradiol has age-dependent changes in patients undergone controlled ovarian hyperstimulation. Were studied 180 cycles of conventional in vitro fertilization. Patients were divided in three groups: Group 1 (age less than 30 years; n = 40), group 2 (age between 30 and 35 years; n = 82), and group 3 (age between 36 and 40 years; n = 58). Leuprolide acetate was used in all cases. Molecular progesterone/estradiol ratio was calculate with the following formula: [Serum progesterone (ng/mL) x 3180 (SI x 10(3) divided by serum estradiol (pg/mL) x 3.671 (SI)]. In patients with age more than 38.5 years there was positive correlation between preovulatory progesterone and estradiol (R = 0.55, R2 = 0.30). There were significant difference in molecular progesterone/estradiol ratio between group 1 compared to group 2 (P less than 0.001), group 1 compared to group 3 (P less than 0.0001), as soon as group 1 compared to group 2 plus group 3 (P less than 0.0001). It is concluded that molecular progesterone/estradiol ratio decreases before any endocrino evidence of ovarian aging. The value of this putative test of ovarian reserve is discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11080941&dopt=Abstract progesterone, progesterone cream



progesterone cream
[Intramuscular vs vaginal progesterone for luteal support in cycles of in vitro fertilization]

[Article in Polish]

Marianowski P, Radwanska E.

I Kliniki Poloznictwa i Ginekologii AM w Warszawie.

OBJECTIVE: To determine the effectiveness of two routes of progesterone supplementation by intramuscular vs. vaginal administration, for luteal phase support of patients undergoing in vitro fertilization (IVF) procedures. SETTINGS: Rush Presbyterian St' Lukes Medical Center and Rush Northshore Medical Center in Chicago, Illinois. MATERIALS AND METHODS: A total of 79 consecutive patients undergoing IVF procedures between August 1997 and July 1998 were assessed; 42 women received progesterone in oil intramuscularly (i.m.)--50-100 mg daily and in 37 patients progesterone was applied as intravaginal gel (80 mg daily), according to patient's preference. STUDY DESIGN: A chart review of the patients' data was performed. There were no statistical differences between the two groups of patients with respect to age, total number of ampoules of gonadotropins used during stimulation, number of oocytes retrieved and fertilized or number of embryos transferred. We then compared pregnancy rates per cycle and pregnancy rates per embryo transferred and miscarriage rates between two groups. Statistical analysis was performed using Student's t test. RESULTS: There were no statistically significant differences between two groups. The pregnancy rate per cycle for i.m. progesterone group was 33% and for vaginal gel group--25% (p = 0.42). Pregnancy rates per embryo transferred were also similar (8% for i.m. group and 5% for vaginal gel group (p = 0.42). Miscarriage rates were also within the same range: 0.083 for vaginal gel and 12% for i.m. group, (p = 0.48). CONCLUSIONS: The route of post-transfer progesterone administration does not appear to affect the pregnancy rate in IVF cycles. Therefore the least expensive and the most convenient route of progesterone administration could be utilized.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11082976&dopt=Abstract progesterone, progesterone cream