Is the expression of the components of the carotid matrix of rats influenced by estrogen, progestin and tibolone? / A expressão dos componentes da matriz carotídea de ratos é influenciada pelo estrogênio, progestagênio e tibolona?

Abstract Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by realtime polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.

Resumo Objetivo Analisar os efeitos do estrogênio isolado ou em combinação com progestogênios e tibolona (TIB) na expressão das metaloproteinases 2 e 9 da matriz extracelular (MMP-2 e MMP-9), da perlecan e da heparanase (HPSE) das paredes vasculares das artérias carótidas. Métodos Trinta ratas Wistar ovariectomizadas com 250 dias de idade foram tratadas oralmente por 5 semanas com: a) 1 mg/kg de benzoato de estradiol (EB); b) EB + 0,2 mg/kg de acetato de medroxiprogesterona (MPA); c) EB + 0,2mg/kg de acetato de noretisterona (NETA); d) EB + 2 mg/kg de didrogesterona (DI); e) 1 mg/kg de TIB; f) placebo (CTR). Após o tratamento, a expressão de mRNA para MMP-2, MMP- 9, e HPSE foi analisada por reação em cadeia da polimerase (RCP) em tempo real, e a expressão de MMP-2, MMP-9, inibidor tecidual de metaloproteinase 2 (TIMP-2), e de perlecan foi quantificado por imunohistoquímica em artérias carótidas. Resultados Os grupos apresentaram diferenças significativas na expressão do mRNA HPSE (p = 0,048), sendo maiores nos grupos EB, EB + MPA e TIB. Não houve diferença estatisticamente significativa nas expressões de mRNA MMP-2 ou MMP-9. A expressão imunohistoquímica de MMP-2, TIMP-2, MMP-9, HPSE e perlecan não mostrou diferenças entre os grupos. Conclusão O estradiol isolado ou associado ao tratamento com MPA e TIB pode aumentar a expressão de mRNA HSPE nas paredes das artérias carótidas em ratas ovariectomizadas.

Lipid profile in females of reproductive age group using injectable contraceptives [progestogen-only]

To determine and compare the values of lipid profile in married fertile females of reproductive age group using injectable contraceptives. Comparative cross sectional study. This study was carried out in the Department of Biochemistry, Postgraduate Medical Institute, Lahore and Lahore General Hospital, Lahore from July 2010 to Dec 2010. A total of 250 married fertile women in their reproductive age were selected. They were divided in two groups: Group 1 [controls] and Group 2 [injectable contraceptive users]. Levels of s erum total cholesterol, serum triglycerides, high density lipoprotein-cholesterol were measured using standard kits. Low density lipoprotein-cholesterol was calculated with Fried Wald equation. Results were analyzed by using student's t test. Informed consent was taken from each patient and control subject for this study. Injectable contraceptives cause significant decrease in HDL-C and significant increase in serum triglycerides and LDL-C. It is suggested that Lipid profile should be estimated before starting every course [the course may be 3-6months] of injectable contraceptives to the subjects

Histomorfometria da mama de ratas tratadas com estrogênio e/ou progestagênio / Breast histomorphometry of rats treated with estrogen and/or progestogen

OBJETIVO: Avaliar as alterações histomorfométricas nas mamas de ratas tratadas com estrogênio e/ou progestagênio por curto período de tempo. MÉTODOS: Foram divididas em quatro grupos 40 ratas ooforectomizadas: GC-recebeu veículo; GE-recebeu benzoato de estradiol (37,6 µg/animal); GP-recebeu acetato de medroxiprogesterona (11,28 mg/animal) e, GEP-recebeu benzoato de estradiol (37,6 µg/animal) e acetato de medroxiprogesterona (11,28 mg/animal). No grupo GE, o estradiol foi administrado durante sete dias, por via subcutânea. Já no grupo EP o estradiol foi administrado nos primeiros sete dias e o progestagênio por mais 23 dias, por via subcutânea. Vinte e quatro horas após a última administração dos hormônios, os animais foram anestesiados e o primeiro par de mamas inguinais removido, imerso em formaldeído a 10 por cento e processado para inclusão em parafina, sendo os cortes corados pela Hematoxilina-Eosina. Foram avaliadas a morfologia e a área ocupada pelo parênquima mamário, sendo os dados submetidos à análise de variância complementado pelo teste de Kruskal-Wallis (p < 0,05). RESULTADOS: As mamas no grupo-controle apresentaram-se atrofiadas, sendo que, nos animais dos grupos GE e GEP, nota-se a presença de alvéolos típicos contendo secreção no seu interior, já nos animais tratados somente com progestagênio (GP) notam-se alvéolos formados por células volumosas que ocupam praticamente todo o lúmen alveolar. A morfometria mostrou haver maior área de parênquima mamário nos animais tratados com hormônios (GE = GP > GEP > GC; p < 0,05) CONCLUSÃO: O estradiol e o progestagênio apresentaram efeito proliferativo no parênquima mamário. No entanto, a administração prévia de estradiol modifica a ação do progestagênio no tecido mamário da rata.

OBJECTIVE: To evaluate the breast histomorphometric changes in rats treated with estrogen and/or progestogen for a short period of time. METHODS: Forty oophorectomized rats were divided into four groups: GC, vehicle; GE, treated with estradiol benzoate (37.6 mg/animal); GP, treated with medroxyprogesterone acetate (11.2 mg/animal) and GEP, treated with estradiol benzoate (37.6 mg/animal) plus medroxyprogesterone acetate (11.28 mg/animal). In GE group, estradiol was administered subcutaneously for seven days; in GEP group, estradiol was administered once in a day for the first seven days and the progestogen over the next 23 days both subcutaneously. Twenty-four hours after the last hormone administration, the animals were killed upon deep anesthesia and the first inguinal breasts were removed, fixed in 10 percent formaldehyde and processed to be included in paraffin, with the sections being stained by hematoxylin-eosin. Morphology and the area occupied by mammary parenchyma were assessed, with the data undergoing analysis of variance followed by the Kruskal-Wallis test (p < 0.05). RESULTS: The control group breasts were found atrophic and, in GE and GEP group animals, typical alveoli with secretion inside are present; in progestogen-treated animals (GP), alveoli formed by large cells occupying almost the entire alveolar lumen are noted. Morphometric analysis showed a larger mammary parenchyma area in hormone-treated animals (GE = GP > GEP > GC; p < 0.05). CONCLUSION: Estradiol and progestogen had a proliferative effect on mammary parenchyma. However, prior estradiol administration changes the progestogen action on rat mammary tissue.

Progestógenos: farmacologia e uso clínico / Progestagens: pharmacology and clinical use

Os progestógenos são esteroides que podem ser sintéticos ou naturais. A progesterona é o único progestágeno natural. Os progestógenos sintéticos tentam mimetizar o efeito da progesterona, e são chamados de progestinas. Cada progestina apresenta diferentes propriedades farmacológicas, dependendo da molécula da qual foi originada, usualmente testosterona e progesterona. Pequenas mudanças estruturais nas moléculas originais levam a diferenças consideráveis na atividade de cada uma das progestinas. O objetivo deste trabalho é revisar a origem dos progestógenos, as peculiaridades de cada grupo e seu uso clínico mais comum. As informações já levantadas sobre o efeito das progestinas em patologias importantes e prevalentes, como o câncer de mama e eventos tromboembólicos, também será abordado.

Progestagens are natural or synthetic steroids, and progesterone is the only natural one. Synthetic progestagens, called progestins, were created to mimic the effects of natural progesterone. The progestins have different pharmacological properties depending on the parent molecule, usually testosterone or progesterone, from which they are derived. Very small structural changes in the original molecule may induce considerable differences in the activity of the derivative. The aim of this paper is to review the origin of each progestin, the peculiarities of each group and its most common clinical use. The current knowledge about the effect of progestins on important and prevalent diseases, such as breast cancer and thromboembolic events, will also be addressed.

Serum copper in rural women taking combined oral contraceptive.

This prospective case-control study included 78 women between 15 to 45 years of age from rural area to see changes in serum copper level as a consequence of oral contraceptive use. Among the subjects, 34 women were included as controls because of not taking any form of hormonal contraceptives neither during the time of selection nor during one-year period prior to the study. Women in the control group were motivated to consume oral pill (Sukhi) for 3 consecutive cycles. At the 3(rd) month, 25 such women became available and henceforth included as cases on longitudinal basis. Another 44 women were randomly selected as cases on the basis of using combined oral contraceptives (Sukhi) for a duration of 4 months onwards. Considering different duration of oral contraceptive (OC) use, subjects were grouped as follows: Group I (n=34)--> controls, Group II (n=25)--> 3 months, Group III (n=17)--> 4 months - 2 years and Group IV (n=27)--> >2 years. Finally, 103 samples of blood (34 from controls and 69 from oral contraceptives users) were collected for estimation of Serum Copper (mgm/dl) by Atomic Absorption Spectrometry using UNICAM-AA Spectrometer. Mean+/-SD of Serum Copper significantly increased in all 3 contraceptive groups in comparison to controls (p<0.001). Further study including larger population from rural area was recommended to see correlation among serum copper and other trace elements with side effects of hormonal contraceptives. This preliminary study tried to explore the possibility of establishing biochemical monitoring of serum trace elements in OC users.

Effects of an oestrogen only and oestrogen progestin regimen of hormone replacement therapy on lipid profile in postmenopausal women

Hormone replacement therapy [HRT], is known to be accompanied by changes in blood lipid profile. The use of a progestin in addition to oestrogen is believed to negate or attenuate the effects of oestrogen on lipids and lipoproteins. In this study, we compared the lipid profiles of two groups of postmenopausal women who had been using the two different types of regimens of HRT. Each group consisted of twenty women. The first group of women consisted of women who had undergone surgical menopause and were using an oestrogen only HRT [Premarin]. The second group consisted of women who had undergone natural menopause and were on a combined, sequential regimen of oestrogen and progestin [Progyluton]. For each group, total cholesterol, triglycerides, VLDL-C, LDLC, HDL-C, ratio were estimated. Certain difference were observed in these parameters of the two groups but statistical analysis showed no significant. Thus our study indicated that the presence of a progestin in HRT may have some effects on lipid profile, but it does not alter it significantly

Effect of medroxyprogesterone acetate on thyrotropin secretion in adult and old female rats

Steroid hormones have been implicated in the modulation of TSH secretion; however, there are few and controversial data regarding the effect of progesterone (Pg) on TSH secretion. Medroxyprogesterone acetate (MPA) is a synthetic alpha-hydroxyprogesterone analog that has been extensively employed in therapeutics for its Pg-like actions, but that also has some glucocorticoid and androgen activity. Both hormones have been shown to interfere with TSH secretion. The objective of the present study was to investigate the effects of MPA or Pg administration to ovariectomized (OVX) rats on in vivo and in vitro TSH release and pituitary TSH content. The treatment of adult OVX rats with MPA (0.25 mg/100 g body weight, sc, daily for 9 days) induced a significant (P<0.05) increase in the pituitary TSH content, which was not observed when the same treatment was used with a 10 times higher MPA dose or with Pg doses similar to those of MPA. Serum TSH was similar for all groups. MPA administered to OVX rats at the lower dose also had a stimulatory effect on the in vitro basal and TRH-induced TSH release. The in vitro basal and TRH-stimulated TSH release was not significantly affected by Pg treatment. Conversely, MPA had no effect on old OVX rats. However, in these old rats, ovariectomy alone significantly reduced (P<0.05) basal and TRH-stimulated TSH release in vitro, as well as pituitary TSH content. The results suggest that in adult, but not in old OVX rats, MPA but not Pg has a stimulatory effect on TSH stores and on the response to TRH in vitro

Effects of depot medroxyprogesterone acetate on the calcium metabolism of adult ovariectomized rats

This paper describes experiments designed to test the effect of depot medroxyprogesterone acetate (DMPA) on calcium metabolism of adult ovariectomized rats. The 24 animals were randomly assigned to control or treated groups. Treated rats received 15 mg of DMPA i.m. per week, during four or twelve weeks. Controls received solvent alone. The variables characterizing the metabolism of Ca (daily rates of intestinal absorption and excretion, bone accretion and resorption and the sizes of the exchangeable pools and their rate constants) were measured with the aid of 45Ca according to Aubert and Milhaud. No effects were observed at four weeks of treatment. After twelve weeks, treatment produced serum levels of 46.5 ñ 5.6 nmoles of medroxyprogesterone/L, reduction of bone turnover (Ca accretion and resorption rates) and of the size of the slow exchanging Ca compartment. The increase in true Ca intestinal absorption was compensated by the increased endogenous fecal Ca excretion. The mass of body Ca was not affected by treatment.

Eficácia, tolerabilidade e controle de ciclo de um novo contraceptivo de baixa dose contendo 75 mcg de gestodeno e 20 mcg de etinilestradiol / Efficacy, tolerability and cycle control of a new low-dose contraceptive containing 75 mcg gestopne and 20 mcg ethinylestradiol

Um estudo multicêntrico foi conduzido em 12 centros brasileiros para avaliar a eficácia, tolerabilidade e controle de ciclo de um novo contraceptivo de baixa dose contendo 75 mc de gestodeno e 20 mcg de etinilestradiol, durante seis ciclos de tratamento. Participaram do estudo 323 mulheres, das quais 272 completaram os seis ciclos de tratamento. Nenhuma gravidez ocorreu entre as usuárias do contraceptivo em estudo. Um total de 1.705 ciclos foi avaliado quanto ao padrao de sangramento. Em 95,2 por cento dos ciclos nao houve spoting nem sangramento de escape. Ocorreu spotting em 3,9 por cento dos ciclos e sangramento de escape em 2,5 por cento dos ciclos. Com relaçao ao número de mulheres, 86,1 por cento nao apresentaram spotting nem sangramento de escape em nenhum momento do ciclo. Observou-se uma diminuiçao significativa, com relaçaoa o pré tratamento, da incidência e intensidade de sinais e sintomas tais como acne, dismenorréia, edema, desconforto mamário, náusea, cefaléia, enxaqueca, tontura, nervosismo, depressao e fadiga. Nao houve variaçao significativa no peso médio ao longo do tratamento. A adesao ao tratamento foi boa, tendo havido esquecimento de tomada de uma ou mais pílulas em apenas 4 por cento de ciclos; 15,8 por cento das mulheres nao completaram o período de seis ciclos de tratamento, sendo que em 5,9 por cento dos casos a razao para descontinuaçao foi atribuída a efeitos adversos. Os resultados permitem concluir pela eficácia contraceptiva, bom controle de ciclo e tolerabiblidade do novo contraceptivo contendo gestodeno associaçao a 20 mcg de etinilestradiol

Relaxant action of androgens, progestins and corticosteroids on the isolated ileum of the guinea pig

La acción de tres diferentes clases de derivados de la progesterona fueron probados sobre las contracciones espontáneas del íleon aislado de cobayo. Los resultados mostraron que este tejido es muy sensible a la acción de los esteroides. Se observó una marcada relajación que fue dependiente de la dosis y diferente para cada compuesto. Esta diferencia fue asociada a la estructura molecular del esteroide. Así, las progestinas 5ß-reducidas fueron las más potentes, seguidas de los andrógenos 5 alfa y 5ß-reducidos. Los compuestos 4-en, 17 alfa-OH-progesterona y los corticosteroides, fueron los más bajos en potencia. La 5alfa-pregnandiona y los pregnandioles fueron prácticamente inefectivos. La gran sensibilidad del músculo liso del íleon permite postular a este órgano como blanco de esteroides. Es posible que en algunas circunstancias fisiológicas, como podría ser el embarazo, los trastornos de motilidad intestinal observados en este estado estén asociados al incremento notable de esteroides circulantes