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Kimberly K. Leslie

Progesterone

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Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange Feb 2013

Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange

Kimberly K. Leslie

No abstract provided.


Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar Feb 2013

Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar

Kimberly K. Leslie

Cancer and its link to reproductive hormones is an area of intense concern for our patients and has been the subject of much speculation. But if estrogen causes breast cancer, for example, most women would eventually develop the disease. We know this is not the case! Actually, estrogen and progesterone have been linked to a decrease as well as an increase in cancer, depending upon the type of tumor under investigation. The purpose of this manuscript is to review the data supporting those relationships.


Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie Feb 2013

Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie

Kimberly K. Leslie

The uterine endometrium responds to unopposed estrogen stimulation with rapid cell proliferation. Progesterone protects the endometrium against the hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2 terminus and may function differently from hPRA. Thus, the relative expression of hPRA:hPRB is likely to be important for the action of progesterone. We hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial cancer …


Estrogens In Intrahepatic Cholestasis Of Pregnancy., Kimberly Leslie, L. Reznikov, F. Simon, P. Fennessey, H. Reyes, J. Ribalta Feb 2013

Estrogens In Intrahepatic Cholestasis Of Pregnancy., Kimberly Leslie, L. Reznikov, F. Simon, P. Fennessey, H. Reyes, J. Ribalta

Kimberly K. Leslie

OBJECTIVE: To determine whether estrogen production and excretion are impaired in gravidas with intrahepatic cholestasis. METHODS: Plasma and urine samples were collected from 13 women from the United States and Chile at 35-38 weeks' gestation with mild (n = 9) or severe (n = 4) intrahepatic cholestasis of pregnancy. Urinary and plasma steroid levels from women with cholestasis were compared with levels from 27 normal pregnant women within the same gestational age range. Urinary concentrations of dehydroepiandrosterone (DHEA), estrone (E1), estradiol (E2), estriol (E3), estetrol, progesterone, and 16-hydroxy-pregnenolone were measured by gas chromatography mass spectrometry, and plasma concentrations of DHEA …


Oestrogen Modulation With Parturition In The Human Placenta., Kimberly Leslie, D. Zuckerman, J. Schruefer, M. Burchell, J. Smith, B. Albertson Feb 2013

Oestrogen Modulation With Parturition In The Human Placenta., Kimberly Leslie, D. Zuckerman, J. Schruefer, M. Burchell, J. Smith, B. Albertson

Kimberly K. Leslie

An initial group of term (36-41 6/7 weeks), preterm (less than 36 weeks), and post-term (42 or more weeks) placentae were collected from women at delivery to determine the placental levels of important steroids and steroidogenic enzymes involved in the oestrogen synthesis pathway as a function of gestational age. A second group of placentae were obtained from women delivering at term before and after the onset of labour. Placentae were evaluated individually for cytosolic steroid hormone levels and microsomal steroidogenic enzyme activities. Oestradiol (E2), oestrone (E1), progesterone (P), and delta-4-androstenedione (A) were measured by radioimmunoassay in placental cytosols. Aromatase (AR), …


Low Serum Estradiol And High Serum Progesterone Concentrations Characterize Hypertensive Pregnancies At High Altitude., S. Zamudio, Kimberly Leslie, M. White, D. Hagerman, L. Moore Feb 2013

Low Serum Estradiol And High Serum Progesterone Concentrations Characterize Hypertensive Pregnancies At High Altitude., S. Zamudio, Kimberly Leslie, M. White, D. Hagerman, L. Moore

Kimberly K. Leslie

OBJECTIVE: Intrauterine growth retardation and preeclampsia are more common at high than at low altitude. Because altered hormonal profiles have been linked with these disorders, we asked whether placental steroid hormone concentrations were altered during pregnancy at high altitude. METHODS: We measured progesterone, unconjugated estradiol, and estriol (by radioimmunoassay) at weeks 20, 30, and 36 of pregnancy in 18 women at low altitude (1600 m) and 40 women at high altitude (3100 m). RESULTS: Women at 3100 m compared with 1600 m had lower serum estradiol concentrations at week 36 of pregnancy, and lower estriol and higher progesterone concentrations throughout …


Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin Feb 2013

Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin

Kimberly K. Leslie

OBJECTIVE: The antiestrogen tamoxifen has been found to be effective in decreasing glioblastoma cell proliferation, but the mechanism underlying this effect and whether it is through the estrogen receptor (ER) is controversial. The objective of this study was to determine whether ERs are present in three human glioblastoma cell lines--HS683, U138MG, and JHN J889H--using the most sensitive techniques available. METHODS: Ligand binding and flow cytometry were employed to identify estrogen and progesterone receptors. The reverse transcriptase-polymerase chain reaction was used to identify ER mRNA, and a novel reporter gene transfection assay demonstrated that the ER was capable of activating gene …


Molecular Tools To Reestablish Progestin Control Of Endometrial Cancer Cell Proliferation., D. Dai, N. Kumar, D. Wolf, Kimberly Leslie Feb 2013

Molecular Tools To Reestablish Progestin Control Of Endometrial Cancer Cell Proliferation., D. Dai, N. Kumar, D. Wolf, Kimberly Leslie

Kimberly K. Leslie

OBJECTIVE: Endometrial cancers often arise in a setting of estrogen stimulation unopposed by the differentiating effects of progesterone. Our laboratory and others have previously shown that progesterone receptor down-regulation or perturbation of progesterone receptor isoform A or B expression is associated with the development of poorly differentiated endometrial cancers that are not growth inhibited by progestins. The purpose of these studies was to reestablish high progesterone receptor isoform A and B gene expressions in such endometrial cancer cells and to examine the effects of progestin treatment on cell growth and metastatic potential after this transformation. STUDY DESIGN: To induce high …


Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie Feb 2013

Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie

Kimberly K. Leslie

The uterine endometrium is exquisitely sensitive to hormones, in particular estrogen and progesterone and to a lesser extent androgens and glucocorticoids. These hormones tightly regulate the complex functioning of the female reproductive tract and are intimately involved in controlling the growth, development, and remodeling of reproductive tissues as well as the cyclic changes that occur during the menstrual cycle. Steroids function by binding to nuclear receptor proteins that act as transcription factors to modulate the expression of genes, though many non-genomic effects for steroids have also been described. An imbalance of the hormones leads to cancer. In particular, endometrial carcinogenesis …