It is the first time in Lithuania that practical application of semen filtration by Sephadex G-15 for the needs of artificial insemination industry was assessed. The efficacy of semen filtration was assessed applying a battery of sperm quality assays to study bovine spermatozoa quality before and after filtration, as well as after cryopreservation. The estimation of effect of different concentrations of progesterone, oestradiol, heparin separately or in combination, on different functional parameters of bull spermatozoa after thawing was performed. These are the first published studies applying integrated approach to study the effects of sperm challenge with several biologically active substances.

Acid-base regulation, as reflected by hydrogen ion concentration ([H+]), and the chemoreflex control of breathing were examined in healthy pre- (PRE; n=20) and postmenopausal (POST; n=15) women of a comparable age (45 ± 2.7 vs. 52 ± 1.8 years). [H+] behaviour was examined in both groups at rest and during exercise above the ventilatory threshold using Stewart’s physicochemical approach to acid-base analysis. Ventilatory chemoreflex characteristics were assessed using Duffin’s modified rebreathing protocol that includes 5 min of prior hyperventilation and maintenance of either hyperoxic (150 mmHg) or hypoxic (50 mmHg) iso-oxia. As expected, the ovarian hormones progesterone ([P4]) and estrogen ([E2]) were significantly lower in the POST group. [H+] was unaffected by menopausal status at rest or during exercise. At rest the POST group exhibited significantly higher PaCO2 and [SID] values relative to the PRE group. In general, the acidifying effects of increased PaCO2 were offset by the alkalizing effect of increases in [SID] (or vice versa) in the POST group such that [H+] did not differ between PRE and POST groups. The central ventilatory chemoreflex also differed between groups with the POST group exhibiting a significantly higher threshold and a lower sensitivity in the response to CO2 relative to the PRE group. [P4] was found to partially account for the significant group differences in acid-base and central ventilatory chemoreflex control characteristics supporting the role of [P4] as an important determinant of acid-base status and the chemical control of ventilation in healthy women. Findings of the current study may have potential relevance in understanding the increased occurrence of various health conditions such as osteoporosis and sleep disordered breathing in females following the onset of menopause. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2007-09-21 08:53:00.841

This study examines the effect of progesterone-only injectable contraceptives, and medroxyprogesterone acetate (Depo-Provera) in particular, on the cells of the uterine cervix. Cervical and vaginal smears were taken before commencement of therapy and at 3 and 6 month intervals thereafter on 79 asymptomatic women attending a family planning clinic. Results of hormonal and cellular measurements before and after therapy were compared. menstrual cycling was also studied. The effect on Methods used were hormonal maturation indices, image analysis measurements and microscopic observation of cellular . features. The latter included anisocytosis, anisokaryosis, karyomegaly , plaque formation, cytoplasmic wrinkling, nuclear grooving, hypertrophy, atrophy, cytoplasmic moulding and density, retarded maturation and nuclear protrusions. Squamous, endocervical and metaplastic cells were examined. Analysis of the results showed that progesterone-only contraceptives produce all of the above to a greater or lesser degree resulting in an increased relative nuclear area which may be confused with intraepithelial neoplasia. This is due to the production of a folate deficiency at target organ level which interferes with cell division and slows the maturation process. This effect enabled further observations to be made leading to the establishment of the origin and content of the nipple-like protrusions which occur in endocervical cells in response to hormonal activity. Physiological effects included amenorrhoea and irregular menstrual cycling. Most women showed evidence of interference with normal cycling to a varying degree. The documented cellular changes were shown to modify the expression of common inflammatory and neoplastic conditions of the uterine cervix. These included trichomoniasis, herpesvirus cervicitis, human papillomavirus infection, folate deficiency, cervical intraepithelial neoplasia and invasive carcinoma as well as multiple pathologies. The potential for diagnostic error was examined. New diagnostic criteria were formulated based on the comparison of cellular features found in the presence of the contraceptive with those found under normal conditions. It is anticipated that these criteria will facilitate the cytological diagnosis of pathological conditions of the uterine cervix in users of depo-medroxyprogesterone acetate (DMPA), leading to increased accuracy and improved and better directed patient management. / Thesis (M.Med.Sc.)-University of Natal, Durban, 1993.

<p>The majority of breast tumors express the estrogen receptor (ER), and more than half of these cancers also express the progesterone receptor (PR). While the actions of ER on breast cancer pathogenesis are well understood, those of PR are still unclear. The Women's Health Initiative trial in 2002 brought into focus the alarming result that women receiving both estrogen and progestins as hormone replacement therapy are at greater risk for breast cancer than women receiving estrogen alone. Thus, there is considerable interest in defining the mechanisms that underlie the pharmacological actions of progestins in the normal and malignant breast. </p><p>Progestins facilitate cell cycle progression through multiple mechanisms, one of which is the induction of phosphorylation of the tumor suppressor retinoblastoma (Rb) protein. Stimulation by growth factors induces the transcription of Cyclin D1 which in turn activates the cyclin dependent kinases (CDKs). The Cyclin D1- Cdk4/6 complex phosphorylates the Rb protein, leading to the release of E2F1, which then binds and activates other target genes, leading to G1-S transition of the cell cycle. Given the reported action of PR to activate MAPK signaling, we initially thought that the progestin-induced Rb phosphorylation was mediated by this pathway. However, we turned to an alternate hypothesis based on our data using MEK inhibitors demonstrating that this was not the case. </p><p>Given the primacy of Cyclin D1 in cell cycle control, we then turned our attention to defining the mechanism by which Cyclin D1 expression is regulated by PR. Interestingly, it was determined that progestin mediated up- regulation of Cyclin D1 is rapid, peaking at 6hrs post hormone addition followed by a decrease in expression reaching a nadir at 18hrs. Unexpectedly, we found that contrary to what has been published before, the induction of Cyclin D1 mRNA expression was a primary transcriptional event and we have demonstrated the specific interaction of PR with PREs (progesterone response elements) located on this gene. We have further determined that the half-life of Cyclin D1 mRNA is decreased significantly by progestin addition explaining how the levels of this mRNA following the addition of hormone are quickly attenuated. Thus, when taken together, our data suggest that progestins exert both positive and negative effects on Cyclin D1 mRNA, the uncoupling of which is likely to impact the pathogenesis of breast cancer</p><p>The observation that PR reduces the Cyclin D1 mRNA stability led us to investigate the effects of PR on RNA binding proteins, especially those which are involved in RNA stability. We discovered that PR induces the expression of several RNA binding proteins. Although the work to determine the effects of these RNA binding proteins on CyclinD1 mRNA stability is still ongoing, we have discovered a role for one of the PR-induced RNA binding proteins tristetraprolin (TTP), in the suppression of the inflammation pathway in breast cancer. We found that while TTP was not required for the PR-mediated decrease in Cyclin D1 mRNA stability, overexpression of this tumor suppressive protein was able to inhibit IL-1&#946;-mediated stimulation of inflammatory genes in our breast cancer model. Since it is established that the upregulation of the inflammatory pathway is oncogenic, we are currently exploring the intersection of PR and TTP-mediated signaling on the inflammation transcriptome in breast cancer. </p><p>Thus, collectively these data provide us with a better picture of the poorly understood actions of PR on breast cancer proliferation and tumorigenesis. We believe that further investigation of the studies developed in this thesis will lead to novel and better-targeted approaches to the use of PR as a therapeutic target in the clinic.</p> / Dissertation

Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain. In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated. In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex. In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5&lt;*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata. Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women. In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1987, härtill 5 uppsastser</p> / digitalisering@umu

The purpose of this study is to investigate the discrepancies of female breast cancer mortality between the Appalachian and Non-Appalachian regions of Kentucky using data from the Kentucky Cancer Registry. This study identified subtype, reproductive, and regional differences in women with breast cancer in Kentucky. Among women with breast cancer living in Kentucky from 2004 to 2007, one and three live births significantly increased a woman’s risk of breast cancer mortality by 91% and 58% respectively, compared to a woman with zero live births. Progesterone receptornegative tumor status significantly increased a woman’s risk of breast cancer mortality by 64% compared to women with progesterone receptor-positive breast cancer. Residence in the Appalachian region significantly increased a woman’s risk of breast cancer mortality by 3.14-fold. After adjusting for regional interactions, progesterone receptor-negative tumor status in the Appalachian region increased a woman’s risk of breast cancer mortality by 3.13-fold. These findings suggest parity and estrogen receptor tumor status do not contribute to the breast cancer differences between the Appalachian and Non-Appalachian region of Kentucky. The association between progesterone receptor status and Appalachian residency suggest factors associated with the Appalachian region provide the poorest prognosis for a woman with breast cancer in Kentucky.

Diss. Linköping : Univ., 2001.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2003. / Härtill 4 uppsatser.