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Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors.

Stavreus-Evers A, Nikas G, Sahlin L, Eriksson H, Landgren BM.

Division for Reproductive Endocrinology, Department of Woman and Child Health, Karolinska Hospital, Huddinge, Sweden. anneli.strsvreus-evers kbh.ki.se

OBJECTIVE: To investigate the relation between the development of endometrial pinopodes and the serum concentration of hormones and the distribution of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B. DESIGN: Prospective clinical study. SETTING: Hospital-based unit of reproductive health and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-seven healthy fertile women with normal menstrual cycles. INTERVENTION(S): Urine and blood sampling for hormone measurement, vaginal ultrasonography, and endometrial biopsy. MAIN OUTCOME MEASURE(S): Appearance of the endometrium on light microscopy, pinopode formation, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and expression of progesterone receptors A and B and estrogen receptors alpha and beta. RESULT(S): Pinopode formation and regression were closely associated with increases and decreases, respectively, in serum progesterone concentration. At pinopode development, levels progesterone receptors A and B in the glandular and luminal epithelial cells decreased; this effect was mainly dependent on the absence of progesterone receptor B. Serum estrogen levels and levels of estrogen receptor alpha and beta did not correlate with pinopode formation. CONCLUSION(S): The increase in serum progesterone level and down-regulation of progesterone receptor B are important in development of pinopodes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11591414&dopt=Abstract progesterone, progesterone cream



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DNA slows dissociation of progesterone receptor-steroid ligand complexes.

Pokrovskaya EV, Levina IS, Kamernitsky AV, Shevchenko VP, Smirnov AN.

Laboratory of Endocrinology, School of Biology, Moscow Lomonosov State University, Lenin Hills 1/12, Moscow 119899, Russia.

Steroid ligands are known to affect the interactions of their respective receptors with DNA. In the present study, the possibility of DNA interference in progesterone receptor-ligand interactions was investigated. An oligonucleotide containing a hormone response element (HRE) was shown to decrease the dissociation rate of complexes of [3H]progesterone or [3H]16alpha,17alpha-cycloalkanoprogesterones with PRs from rabbit and rat uterine cytosol. The extent to which the oligonucleotide affected the dissociation constant varied from about 4- to 1.5-fold depending on the ligand structure and was ranked in the following order: progesterone>16alpha,17alpha-cyclopropanoprogesterone approximately 16alpha,17alpha-cyclopentanoprogesterone>/=16alpha,17alpha-cyclohex-2'-enoprogesterone approximately 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone>/=16alpha,17alpha-cyclohexanoprogesterone. The control oligonucleotide lacking HRE had a weak effect, if any, on the dissociation kinetics. No influence of the HRE-containing oligonucleotide on the equilibrium binding of ligands to PR was observed. The results suggest that the DNA partner affects binding of PR to its ligand.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12787896&dopt=Abstract progesterone, progesterone cream



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Effect of high progesterone concentrations during the early luteal phase on the length of the ovulatory cycle of goats.

Menchaca A, Rubianes E.

Department of Physiology, Faculty of Veterinary Sciences, Lasplaces 1550, 11600, Montevideo, Uruguay.

The effect of exogenous progesterone exposure early in the oestrous cycle on the duration of the interovulatory interval was studied in dairy goats. A controlled intravaginal drug release (CIDR-G) device was inserted for 5 days starting at day 0 (D0 group, n=6) or day 3 (D3 group, n=5) postovulation. A third group was composed of untreated control goats (control group, n=7). Daily transrectal ultrasound was carried out during the interovulatory interval to assess the ovarian dynamics. Oestrous behaviour was checked twice a day and serum progesterone levels were assayed in daily jugular blood samples. Treated goats showed two different responses. In three D0 goats and one D3 goat, progesterone concentrations fell immediately after CIDR withdrawal and this was followed by oestrus and ovulation between days 8 and 11 (short cycles). In the other three D0 goats and in four D3 goats the treatment significantly reduced the interovulatory interval (18.3+/-0.3 and 18.5+/-0.3 days, respectively) (shortened cycles) compared with the control group (20.0+/-0.2 days; P<0.05), but the intervals with progesterone concentrations over 1 ng/ml were not different (15.7+/-0.3, 15.8+/-0.7 and 16.0+/-0.5 days for D0, D3 and control goats, respectively). In all D0 goats with a short cycle response, the ovulatory follicle arose from the first follicular wave but in the D3 goat with a short cycle it arose from the second follicular wave. These results showed that premature progesterone exposure early in the ovulatory cycle of the goat affected its length inducing short or shortened cycles. The effect of progesterone could either affect luteotropic support of the corpus luteum (CL) and/or stimulate a premature release of the luteolysin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11600275&dopt=Abstract progesterone, progesterone cream



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Serum cortisol and 17-hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory?

Charmandari E, Matthews DR, Johnston A, Brook CG, Hindmarsh PC.

London Center for Pediatric Endocrinology, University College London, London W1T 3AA, United Kingdom. charmane mail.nih.gov

One of the main aims in the management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency is to achieve adequate suppression of the adrenal cortex with the smallest possible dose of glucocorticoid substitution. To evaluate the administration schedule of current replacement therapy regimens, we investigated the cortisol-17-hydroxyprogesterone interrelation in 36 patients (13 males and 23 females; median age, 12.3 yr; range, 6.1-18.8 yr) with salt-wasting congenital adrenal hyperplasia. As sufficient variation in 17-hydroxyprogesterone concentrations was required to allow analysis of the cortisol-17-hydroxyprogesterone interrelation, patients were divided into 2 groups depending on the adequacy of hypothalamic-pituitary-adrenal axis suppression. The first group consisted of 17 patients with suppressed 17-hydroxyprogesterone concentrations (group 1), and the second group consisted of 19 patients with nonsuppressed 17-hydroxyprogesterone concentrations (group 2). We determined serum cortisol and 17-hydroxyprogesterone concentrations at 20-min intervals for a total of 24 h while patients were receiving their usual replacement treatment with hydrocortisone and 9alpha-fludrocortisone. We also determined the lowest dose of dexamethasone required to suppress the 0800 h serum ACTH concentrations when administered as a single dose (0.3 or 0.5 mg/m(2)) the night before. Mean 24-h cortisol and 17-hydroxyprogesterone concentrations were 3.9 microg/dl (SD = 2.1) and 66.2 ng/dl (SD = 92.7), respectively, in group 1 and 4.1 microg/dl (SD = 2.5) and 4865.7 ng/dl (SD = 6951) in group 2. The 24-h 17-hydroxyprogesterone concentrations demonstrated circadian variation, with peak values observed between 0400-0900 h. In group 2, 17-hydroxyprogesterone concentrations decreased gradually in response to the rise in cortisol concentrations during the day, but remained low during the night despite the almost undetectable cortisol concentrations between 1600-2000 h. Mean 0800 h androstenedione concentrations correlated strongly with integrated 17-hydroxyprogesterone concentrations (r = 0.81; P < 0.0001), but not with integrated cortisol concentrations. There was a significant negative correlation between cortisol and 17-hydroxyprogesterone at lag time 0 min (r = -0.187; P < 0.0001), peaking at lag time 60 min (r = -0.302; P < 0.0001), with cortisol leading 17-hydroxyprogesterone by these time intervals. Finally, 0800 h serum ACTH concentrations were sufficiently suppressed after a dexamethasone dose of 0.3 mg/m(2) in all but three patients. These findings indicate that in classic 21-hydroxylase deficiency, hydrocortisone should be administered during the period of increased hypothalamic-pituitary-adrenal axis activity, between 0400-1600 h, with the biggest dose given in the morning. Blood investigations performed as part of monitoring of congenital adrenal hyperplasia patients should include androstenedione and 17-hydroxyprogesterone concentrations determined in the morning before the administration of hydrocortisone. It should also be emphasized that blood investigations are only complementary to the overall assessment of these patients, which is primarily based on the evaluation of growth and pubertal progress.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11600525&dopt=Abstract progesterone, progesterone cream



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Laryngeal pyogenic granulomas do not express oestrogen or progesterone receptors.

Marrinan MS, Myssiorek D, Fuchs A, Wasserman P.

Department of Otolaryngology and Communicative Disorders, The Long Island Jewish Medical Center, the Long Island Campus of the Albert Einstein College of Medicine, New Hyde Park, New York, USA 11040, USA.

The objective of this study was to determine the presence of oestrogen and/or progesterone receptors in laryngeal pyogenic granulomas and the impact of these receptors on recurrence of pyogenic granulomas. Twenty-two consecutive patients who underwent microlaryngoscopy and removal of pyogenic granulomas were studied retrospectively. The indications for surgery were airway compromise, failure of medical therapy and suspicion of malignancy. Twelve of these patients' granulomas were analysed for oestrogen and progesterone receptors. Charts were analysed for age, sex, location of the lesion, history of trauma, intubation or gastroesophageal reflux disease (GORD), airway symptoms and recurrence. Oestrogen/progesterone receptors were analysed following deparaffinization of specimens and immunostaining with prediluted anti-oestrogen receptor monoclonal antibody and anti-progesterone receptor monoclonal antibody. No sample expressed oestrogen or progesterone receptors. There were too few recurrences to detect if lack of these receptors played any role in determining outcome in this group. Most of the patients had a history of GORD, intubation or laryngeal surgery. There were 12 recurrences in four patients. All of the recurrences improved on prolonged courses of omeprazole. Pyogenic granulomas do not possess oestrogen or progesterone receptors and are unlikely to respond to hormonal therapy. Patients who have, or are being operated on for, laryngeal pyogenic granulomas should be placed on proton pump inhibitors to decrease the likelihood of recurrence.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11667991&dopt=Abstract progesterone, progesterone cream



progesterone cream
Evidence of progesterone receptors in the mucosa of the urinary bladder.

Rizk DE, Raaschou T, Mason N, Berg B.

Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain.

OBJECTIVE: To investigate whether progesterone receptors are present in the mucosa of the urinary bladder of continent premenopausal women compared with continent postmenopausal women. MATERIALS AND METHODS: Fifty-seven biopsies from the mucosa of the trigone and lateral wall of the urinary bladder were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen and progesterone receptors. The specimens were obtained at cystoscopy performed to investigate hematuria in 42 patients and neoplasia in 15. The study group (n = 29) comprised non-pregnant premenopausal women in the luteal phase of their menstrual cycle and the control group (n = 28) comprised postmenopausal women. None of the subjects had urinary incontinence or was taking medication with hormones. In no case did the primary lesion involve the specimen used for laboratory analysis. RESULTS: There was positive immunostaining with estrogen in 28 patients of the study group (96.5%) and 4 (14.4%) in the control group (p<0.0001). The 28 samples of the study group also showed positive immunostaining for progesterone receptors. There was positive immunostaining with progesterone in 18 samples (64.3%) of the control group (p<0.01). Fourteen samples (50%) of the control group thus showed positive immunostaining for progesterone but no evidence of positive immunostaining with estrogen. Immunostaining for estrogen and progesterone receptors was similar in trigonal and lateral wall samples. CONCLUSION: In continent pre- and post-menopausal women, a direct progestogenic effect on the mucosa of the urinary bladder seems likely in addition to estrogen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11676357&dopt=Abstract progesterone, progesterone cream



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In vivo inhibition of keratinocyte growth factor receptor expression by estrogen and antagonism by progesterone in the mouse mammary gland.

Imagawa W, Pedchenko VK.

Department of Molecular and Integrative Physiology, and Kansas Cancer Institute, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. wimagwa kumc.edu

Mammary gland development is regulated by complex interactions among mammogenic hormones and locally derived paracrine growth factors. In epithelial tissues, keratinocyte growth factor (KGF or FGF-7) originates in the stroma while its receptor (KGFR or FGFR2-IIIb) is present only in the epithelium. Previous work showed that estrogen but not progesterone could stimulate the synthesis of KGF in mammary stroma in vivo. The effects of 17 beta-estradiol and progesterone on KGFR expression in vivo were examined in these studies. Peripubertal and mature virgin mice received subcutaneous injections of hormone in sesame oil after which KGFR mRNA levels were assayed by ribonuclease protection analysis of mammary gland RNA. Estradiol treatment caused a dose- and time-dependent decrease in KGFR mRNA level in mice from both age groups while stimulating ductal growth after 7 days of treatment. Inhibition of KGFR expression was near maximal at an estradiol dose of 2 microg after 1 day of treatment. Progesterone injection increased KGFR mRNA levels but this effect correlated with the stimulation of ductal growth. However, when progesterone was co-administered with estradiol, KGFR mRNA levels were maintained in the absence of any effect on ductal growth. Thus, estradiol inhibited KGFR mRNA only when elevated unopposed by progesterone. These data show that KGFR expression is determined by the ratio of estradiol and progesterone and suggests a mechanism through which these hormones can co-operate to optimize their growth-promoting effects. Consequences of hormone imbalance are also implicated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11691652&dopt=Abstract progesterone, progesterone cream