Postnatal Exposure to Exogenous progesterone Exacerbates the Prenatally-Induced Abnormal Sperms Production and Function in Rats / La exposición Posnatal a la Progesterona Exógena Exacerba la Producción y Función Anormales de Espermatozoides Inducidas Prenatalmente en Ratas

SUMMARY: This study aimed at clarifying the impact of long-term prenatal and postnatal exposure to exogenous progesterone on sperm production and function, relative sex organs weights, and the levels of the relevant hormones in rats. Sixty male Wistar rats were included and classified into three groups (n=20 in each). A test I group had mature rats born to dams treated with progesterone prenatally. A test II group included rats exposed to progesterone during prenatal as well as postnatal periods, and a control group had rats treated with a placebo (olive oil). The test groups revealed a significant reduction in sperm count, motility, and viability with higher abnormal forms than the control group (P< 0.05). Similarly, the test groups revealed significantly lower serum testosterone and higher FSH and LH levels (P< 0.001). Interestingly, the test II group showed pronounced sperm abnormalities, an alarming decrease in sperm viability and motility, and a significant accretion in the relative testicular weight compared to the test I group (p <0.001). Long-term (prenatal and early postnatal) treatment with synthetic progesterone hurts sperm quantity and quality, adversely affecting future male fertility.

Este estudio tuvo como objetivo aclarar el impacto de la exposición prenatal y posnatal a largo plazo a la progesterona exógena en la producción y función de los espermatozoides, el peso relativo de los órganos sexuales y los niveles de las hormonas relevantes en ratas. Sesenta ratas macho Wistar fueron incluidas y clasificadas en tres grupos (n=20 en cada uno). Un grupo de prueba I tenía ratas maduras nacidas de madres tratadas con progesterona prenatalmente. Un grupo de prueba II incluyó ratas expuestas a progesterona durante los períodos prenatal y posnatal, y un grupo de control tenía ratas tratadas con un placebo (aceite de oliva). Los grupos de prueba revelaron una reducción significativa en el recuento, la motilidad y la viabilidad de los espermatozoides con formas anormales más altas que el grupo de control (P < 0,05). De manera similar, los grupos de prueba revelaron niveles significativamente más bajos de testosterona sérica y niveles más altos de FSH y LH (P < 0.001). Curiosamente, el grupo de prueba II mostró anormalidades espermáticas pronunciadas, una disminución alarmante en la viabilidad y motilidad de los espermatozoides y una acumulación significativa en el peso testicular relativo en comparación con el grupo de prueba I (p <0.001). El tratamiento a largo plazo (prenatal y posnatal temprano) con progesterona sintética daña la cantidad y la calidad del esperma, lo que afecta negativamente la futura fertilidad masculina.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

The effects of progesterone on hypoxic ischemic injuries in the Cornu Ammonis (CA) region of the hippocampus of neonatal rats / Efectos de la progesterona en lesiones por hipoxia isquémica en la región Cornu Ammonis (CA) del hipocampo en ratas neonatas

Hypoxia-ischemia (HI) is a major cause of brain damage in the newborn. Several studies elicited the neuroprotective effects of progesterone in adult rats but there is very little literature available on neonatal rats. Therefore the present study is undertaken to see the effect of progesterone in hypoxic ischemic brain injury in neonatal rats, using an established neonatal HI rat pup model. Seven-day-old rat pups were subjected to right common carotid artery ligation and then 60 minutes hypoxia. The first dose of progesterone to treatment group was administered by peritoneal injection (4 mg/kg), after 10 minutes of exposure and subsequent doses were given by subcutaneous injection at 6 h, 24 h and 48 h intervals. Control group was also exposed to HI and was given only the vehicle (peanut oil) through the same route and intervals as that of treatment group. After 96 h, the pups were perfused with 10% formalin and brains were sampled and stained with toluidine blue. Cells density and number of pyramidal cells of the hippocampal Cornu Ammonis (CA) regions were examined by stereological methods. The histomorphometric assessment of the effects of progesterone showed minimal but no significant protective value in the volume, cells density and total number of pyramidal cells of hippocampal CA region of the treatment and control groups (p>0.05) after HI. Our results concluded that 4 mg/kg of PROG had no significant neuroprotective effect in HI model of the neonatal rat's hippocampus.

La hipoxia-isquémica (HI) es una causa importante de daño cerebral en el recién nacido. Varios estudios indican los efectos neuroprotectores de la progesterona en ratas adultas, sin embargo existe poca literatura disponible en ratas recién nacidas. Por tanto, el presente estudio se llevó a cabo para ver el efecto de la progesterona en la lesión cerebral HI en ratas recién nacidas, utilizando un modelo de cría de rata neonata HI establecido. A los siete días de nacidas, las crías de ratas fueron sometidas a la ligadura de la arteria carótida común derecha y luego 60 minutos de hipoxia. La primera dosis de progesterona fue administrada al grupo de tratamiento mediante inyección peritoneal (4 mg/kg), después de 10 minutos de exposición y las dosis posteriores fueron administradas por inyecciones subcutáneas en intervalos de 6 h, 24 h y 48 h. El grupo control también fue expuesto a HI y se le administró solamente aceite de cacahuete a través de la misma ruta y con los intervalos que recibió el grupo de tratamiento. Después de 96 h, las crias fueron perfundidas con formalina al 10% y se tomaron muestras de los cerebros, los que se tiñeron con azul de toluidina. La densidad celular y el número de células piramidales de las regiones del hipocampo Cornu Ammonis (CA) fueron examinadas por métodos estereológicos. La evaluación histomorfométrica de los efectos de la progesterona mostró un valor protector mínimo, pero no significativo en el volumen, densidad de las células y el número total de células piramidales de la región de CA del hipocampo de los grupos de tratamiento y control (p>0,05) después de HI. En conclusión, nuestros resultados indican que 4 mg/kg de progesterona no tuvo efecto neuroprotector significativo en el modelo de HI del hipocampo de ratas neonatas.

Efeitos adversos em usuárias de implante contraceptivo / Adverse effects on contraceptive implant users

A gravidez indesejada continua a ser um grave problema de saúde pública em todo o mundo. Uma das explicações para a manutenção de altas taxas de gestações não planejadas relaciona-se com os efeitos adversos provocados por grande parte dos métodos contraceptivos disponíveis que levam as usuárias a descontinuar seu uso. Nos últimos anos, tem se visto um aumento nas opções de contracepção para garantir métodos mais eficazes, com maiores taxas de continuação e níveis elevados de satisfação da paciente. Entre os métodos contraceptivos de longa ação e com rápida reversibilidade, o implante é considerado um dos mais eficazes e mais seguros. Dentre os efeitos adversos relacionados com esse tipo de contracepção, estão incluídos: alterações no padrão do sangramento, cefaleia, aumento do peso, acne, mastalgia, labilidade emocional e dor abdominal. Portanto, no presente estudo, fez-se uma atualização sobre os possíveis efeitos colaterais desse contraceptivo, visando a um melhor aconselhamento pelos profissionais de saúde antes da inserção desse método, a fim de garantir melhor adesão a ele. Estudos demonstram que um aconselhamento claro antes de iniciar um método de longa duração como o implante subdérmico é imprescindível para melhorar a satisfação e a adesão ao método contraceptivo.

Unwanted pregnancy remains a serious public health problem worldwide. An explanation for keeping high rates of unplanned pregnancies is related to the adverse effects caused by most of the available contraceptive methods that lead users to discontinue its use. In recent years, it has been seen an increase in contraceptive options to ensure the most effective methods with higher continuation rates and high levels of patient satisfaction. Among the long-acting contraceptive methods with rapid reversibility, the implant is considered one of the most effective and safest ways. Among the adverse effects associated with the drug are included: changes in the pattern of bleeding, headache, weight gain, acne, breast pain, emotional lability and abdominal pain. Therefore, in our study it was made an update review on possible side effects of contraception, seeking a better counseling by health professionals before insertion in order to ensure better adherence to the method. Studies show that clear advice before starting long duration method as subdermal implant is essential to improve the satisfaction and adherence to contraception.

Influence of category-heifers, primiparous and multiparous lactating cows-in a large-scale resynchronization fixed-time artificial insemination program

This study was conducted to evaluate the influence of category (heifers, primiparous or multiparous cows) on pregnancy rates in a large scale resynchronization ovulation program. Nelore heifers (n = 903), primiparous lactating cows (n = 338) and multiparous lactating cows (n = 1,223) were synchronized using a conventional protocol of estradiol/P4-based fixed-time artificial insemination (FTAI). Thirty days after ultrasonography, females who failed the first FTAI were resynchronized with the same hormonal protocol prior to a second FTAI. The pregnancy status of each cohort was evaluated by ultrasonography 30 days after each FTAI. The average conception rate after the first FTAI and resynchronization was 80.5%. Heifers had a higher conception rate (85%) than primiparous (76%) or multiparous cows (78%; p = 0.0001). The conception rate after the first FTAI was similar among heifers (57%), primiparous cows (51%) and multiparous cows (56%; p = 0.193). After the second FTAI, heifers exhibited a higher conception rate (66%) than primiparous or multiparous cows (51%; p = 0.0001). These results demonstrate the feasibility of resynchronization in large beef herds for providing consistent pregnancy rates in a short period of time. We also demonstrated that ovulation resynchronization 30 days after FTAI is particularly effective for heifers, providing a conception rate of up to 66%.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Culture of bovine ovarian follicle wall sections maintained the highly estrogenic profile under basal and chemically defined conditions

Follicle cultures reproduce in vitro the functional features observed in vivo. In a search for an ideal model, we cultured bovine antral follicle wall sections (FWS) in a serum-free defined medium (DM) known to induce 17β-estradiol (E2) production, and in a nondefined medium (NDM) containing serum. Follicles were sectioned and cultured in NDM or DM for 24 or 48 h. Morphological features were determined by light microscopy. Gene expression of steroidogenic enzymes and follicle-stimulating hormone (FSH) receptor were determined by RT-PCR; progesterone (P4) and E2 concentrations in the media were measured by radioimmunoassay. DM, but not NDM, maintained an FWS morphology in vitro that was similar to fresh tissue. DM also induced an increase in the expression of all steroidogenic enzymes, except FSH receptor, but NDM did not. In both DM and NDM, there was a gradual increase in P4 throughout the culture period; however, P4 concentration was significantly higher in NDM. In both media, E2 concentration was increased at 24 h, followed by a decrease at 48 h. The E2:P4 ratio was higher in DM than in NDM. These results suggest that DM maintains morphological structure, upregulates the expression of steroidogenic enzyme genes, and maintains steroid production with a high E2:P4 ratio in FWS cultures.

Effect of Combined Sex Hormone Replacement on Bone/Cartilage Turnover in a Murine Model of Osteoarthritis

BACKGROUND: Estrogens act on estrogen receptors distributed in articular cartilages, synovial membrane, and ligaments, which are thought to be related with degenerative changes. Meanwhile, progesterone is known to have a weak anabolic action on bone formation This study evaluates the effects of estrogen and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats. METHODS: Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided into 5 groups and then ovariectomized bilaterally except the sham control group. The first and the second group acting as controls did not receive hormonal therapy, the third group received estrogen, the fourth group received progesterone, and the fifth group received combination of both hormones 10 weeks after surgery. Evaluations were done using the serum levels of cartilage oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C-telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks after OVX and histology using the Osteoarthritis Research Society International (OARSI) osteoarthritis (OA) cartilage histopathology assessment system. RESULTS: Significantly less cartilage degradation (decreased levels of COMP) was found in the combined hormone treated group in comparison with OVX group. Similarly, both hormonal treatment resulted in increased bone formation and decreased bone resorption i.e., a low overall bone turnover status (decrease in the serum OC and CTX-1 levels). CONCLUSIONS: Combined estrogen and progesterone therapy was found to be convincing in terms of reducing the severity of OA in this experimental model.

Moduladores seletivos dos receptores da progesterona: revisão da literatura / Selective modulators of progesterone receptors: literature review

Os moduladores seletivos dos receptores da progesterona (MSRP) são substâncias sintéticas derivadas dos esteroides que têm a capacidade de ocupar os receptores da progesterona e passam a ter ação como antagonista, agonista-antagonista ou agonista desse hormônio, dependendo do tecido alvo. Essas variedades de ações favorecem a utilização dessas substâncias para o tratamento da miomatose uterina, endometriose, entre outros, tendo também importante aplicação na anticoncepção e na reprodução assistida. O mecanismo de ação dos MSRP não está completamente elucidado, uma vez que intercalam efeitos sinérgicos e antagônicos aos da progesterona. Entretanto, sabe-se que têm efeito antiproliferativo, antiangiogênico, aumentam os índices de apoptose celular e promovem uma diminuição do aporte sanguíneo das artérias uterinas e dos vasos espiralados do endométrio. O tempo de utilização dessas drogas é restrito devido aos seus efeitos adversos relacionados, principalmente, alterações endometriais, propriedades abortivas de alguns compostos e efeitos adversos associados com a dose e a utilização em longo prazo.

The selective modulators of progesterone receptors (MSRP) are synthetic compounds derived from steroids that have the ability to bind the progesterone receptor. These substances can act as an antagonist, agonist-antagonist or agonist of the progesterone, and these effects are specific for each target tissue. These properties favor the use of these substances for the treatment of uterine fibroids and endometriosis. These componds can also be used in assisted reproduction and contraception. The precise mechanism by which MSRP acts is not fully understood. However, it is known that these componds have antiproliferative and antiangiogenic effects. Also, MSRP promotes an increase in the rates of apoptosis and decreased blood supply of uterine arteries and vessels of the endometrium. The time of use of these drugs is restricted due to its adverse effects mainly related to endometrial changes, its abortion properties, and adverse effects associated with dose and long-term use.

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.

Expression and regulation of Enpp2 in rat uterus during the estrous cycle

Ectonucleotide pyrophosphatase/phosphodiestrase 2 (Enpp2) isolated from the supernatant of human melanoma cells is a lysophospholipase D that transforms lysophosphatidylcholine into lysophospatidic acid. Although multiple analyses have investigated the function of Enpp2 in the hypothalamus, its role in the uterus during the estrous cycle is not well understood. In the present study, rat uterine Enpp2 was analyzed by RT-PCR, Western blotting, and immunohistochemistry. Quantitative PCR analysis demonstrated that uterine Enpp2 mRNA was decreased during estrus compared to proestrus and diestrus. To determine whether uterine Enpp2 expression is affected by sex steroid hormones, immature rats were treated with 17beta-estradiol (E2), progesterone, or both on postnatal days 14 to 16. Interestingly, the expression of Enpp2 mRNA and protein were down-regulated by E2 in the uterus during estrus but not during proestrus or diestrus, suggesting that Enpp2 may play a role in uterine function during estrus. Enpp2 is primarily localized in the stromal cells of the endometrium during proestrus and estrus. During diestrus, Enpp2 was highly expressed in the epithelial cells of the endometrium. Taken together, these results suggest that uterine Enpp2 may be regulated by E2 and plays a role in reproductive functions during female rat development.

Influence of progesterone on GAD65 and GAD67 mRNA expression in the dorsolateral striatum and prefrontal cortex of female rats repeatedly treated with cocaine

Female rats are intensely affected by cocaine, with estrogen probably playing an important role in this effect. Progesterone modulates the GABA system and attenuates the effects of cocaine; however, there is no information about its relevance in changing GABA synthesis pathways after cocaine administration to female rats. Our objective was to investigate the influence of progesterone on the effects of repeated cocaine administration on the isoenzymes of glutamic acid decarboxylase (GAD65 and GAD67) mRNA in brain areas involved in the addiction circuitry. Ovariectomized, intact and progesterone replacement-treated female rats received saline or cocaine (30 mg/kg, ip) acutely or repeatedly. GAD isoenzyme mRNA levels were determined in the dorsolateral striatum (dSTR) and prefrontal cortex (PFC) by RT-PCR, showing that repeated, but not acute, cocaine decreased GADs/β-actin mRNA ratio in the dSTR irrespective of the hormonal condition (GAD65: P < 0.001; and GAD67: P = 0.004). In the PFC, repeated cocaine decreased GAD65 and increased GAD67 mRNA ratio (P < 0.05). Progesterone replacement decreased both GAD isoenzymes mRNA ratio after acute cocaine in the PFC (P < 0.001) and repeated cocaine treatment reversed this decrease (P < 0.001). These results suggest that cocaine does not immediately affect GAD mRNA expression, while repeated cocaine decreases both GAD65 and GAD67 mRNA in the dSTR of female rats, independently of their hormonal conditions. In the PFC, repeated cocaine increases the expression of GAD isoenzymes, which were decreased due to progesterone replacement.

[Effects of estrogen progesterone on endometrial glycocalyx expression in superovulated mice in the implantation window time]

It has been reported that apical glycocalyx expression of uterine affects embryo implantation. The aim of this study was to determine endometrial glycocalyx and endometrial thickness after estrogen and progesterone injection in hyperstimulated mice at luteal phase. Adult male and female mice were used for induction of pesudopregnancy. The mice were divided into two groups experimental and control groups. Female mice in the experimental group were superovulated and were then mated with vasectomised mice to induce psudopregnancy Experimental group based on hormone injection was subdivided into five groups 1] Estrogen, 2] Progesterone, 3] Estrogen + Progesterone, 4] Antiprogesterone + Estrogen, 5] Sham. Pesudopregnancy in the control group was achieved without any hyperstimulation. The uterines of all groups were collected after 4.5 days of pregnancy and prepared for the assessment of endometrial thickness and endometrial glycocalyx expression. The results showed that estrogen and progesterone injection increased the intensity of PAS reaction, whereas progesterone decreased this. Also our results showed that the endometrial thickness in the sham group was the highest and in the progesterone group was the lowest Our results showed that addition of estrogen to progesterone, compared to P supplementation alone, provided appropriate endometrial conditions to embryo implantation. Hence combination of estrogen and progesterone injection as luteal support hormones can be used in IVF protocols

[Effect of combined administration of estrogen and progesterone on brain edema and neurological outcome after traumatic brain injury in female rats]

Many studies have shown uncontrolled brain edema to be the cause of disabilities and deaths following head trauma. Current data also suggests that a single administration of estrogen or progesterone can have neuroprotective effects on brain injury. In this study we investigated the combined effect of estrogen and progesterone on brain edema and neurological outcomes following traumatic brain injury [TBI] in female rats This interventional-experimental study was performed on 8 groups of female rats as follows: 1- control, 2-Sham, 3-Ovarectomized trauma [TBI+OVX] 4-Vehicle 5-Physiologic dose of estrogen + physiologic dose of progesterone [E1+P1], 6- physiologic dose of estrogen+pharmacologic dose of progesterone [E1+P2] 7-Pharmacologic dose of estrogen+physiologic dose of progesterone [E2+P1] and 8-Pharmacologic dose of estrogen+pharmacologic dose of progesterone [E2+P2]. Hormones were injected i.p, half an hour after diffuse traumatic brain injury through marmarou model to 2 week old ovarectomized rats. Brain edema [via brain water content], blood-brain barrier permeability [via extra vascular evans blue dye] and neurological outcome [via veterinary coma scale] were measured in this animals The results showed significance decreases of 2.68% and 2.88% in water content in group 8 compared to the vehicle group and group 6 respectively and a significant decrease of 2.29% in water content in group 5 compared to group 6. Evans blue level showed significant decreases of 14.7% and 21.1% in groups 6 and 7 compared to the vehicle group. Neurological scores showed a significant increase of 2.5 and 2 in group 5 compared to the vehicle group and group 3, 1 hour after TBI respectively a significant increase was seen in all groups compared to group 3 at 4 and 24 hours after TBI. Scores showed a significant increase of 1.2 in groups 7 and 8 compared to the vehicle group at 24 hours following the TBI. Based on these results, it can be concluded that combined administration of estrogen and progesterone have beneficial effects on both the reduction of brain edema and the neurological outcomes, the improvement depending on what dose of estrogen is administered with progesterone

Progesterona e prevenção do parto prematuro: aspectos atuais / Progesterone and prevention of preterm delivery: and up-to-date report

A incidência de parto pré-termo varia de 7 a 11 porcento de todas as gestações e o nascimento prematuro é uma das principais causas de morbidade e mortalidade neonatal responsável por mais de dois terços das mortes neonatais por malformações congênitas. Objetivando reduzir as taxas de partos prematuros, inúmeras estratégias foram adotadas, entre estas, o uso profilático de progesterona ressurgiu como importante método terapêutico. Entre as principais ações desse hormônio, cita-se o efeito relaxante sobre a musculatura uterina, a capacidade de bloquear os efeitos da ocitocina, ação antiinflamatória e imunossupressora. Estudos recentes concluíram que a utilização de progesterona exôgena reduz as taxas de prematuridade em pacientes com risco de parto prematuro tais como história prévia de parto prematuro e aquelas com colo uterino curto demonstrado pela ultra-sonografia transvaginal no segundo trimestre de gestação. O objetivo desta revisão é, inicialmente, descrever os prováveis mecanismos de ação da progesterona, as suas principais vias de administração e seus efeitos adversos e, posteriormente, avaliar os principais estudos em pacientes assintomáticas e sintomáticas.

The incidence of preterm delivery is about 7 to 11 of all pregnant women and the preterm birth is one the most important cause of neonatal morbidity and mortality. Preterm birth accounts for two thirds of neonatal mortality when fetal malformation is excluded. In order to reduce the preterm birth rate several strategies have been adopted, including the prophylactic using of progesterone. The main effects of this hormone are uterine muscle relaxation, blockage of oxytocin effects, anti-inflammatory properties and immunosuppressing effects in pregnancy. More recently, studies have concluded that the administration of prophylactic progesterone could reduce the preterm birth rate of high risk patients, including previous history of preterm birth and short cervical length at transvaginal scan at mid-trimester pregnancy. The purpose of this review is, firstly, to describe the possible mechanism of action of progesterone, its route of administration and its side-effects and, secondly, assess the most recent studies in both asymptomatic and symptomatic patients.

Manipulation of cytokine production profiles as a therapeutic approach for immunologic pregnancy loss.

Pregnancy is not as successful as one might think; it can be compromised by several complications such as recurrent spontaneous miscarriage, pre-term delivery, pre-eclampsia etc. Much attention has been paid to the possibility of the maternal immune system mediating deleterious effects on pregnancy. Research conducted during the last two decades has shed much light on cell-mediated immunologic effectors that might underlie these pregnancy complications. Of particular interest are the effects that pro-inflammatory and anti-inflammatory cytokines have on the foetus and placenta, and thus on the success and failure of pregnancy. This review presents evidences that certain cytokine profiles are associated with recurrent miscarriage and pre-term delivery and discusses possible pathways of effector function of cytokines in pregnancy loss and the redirection of cytokine profiles from one that is antagonistic to pregnancy towards one that is conducive to the success of pregnancy. Among the promising agents for the modulation of the Th1/Th2 balance are progestogens like progesterone and dydrogesterone; this review also discusses recent evidence that progestogens are capable of modulating cytokine production patterns in pregnancy loss.

[ effect of sex steroid hormones on brain edema and intracranial pressure after experimental traumatic brain injury in rats]

We investigated the role of sex hormones on changes in brain edema intracranial pressure [ICP], cerebral perfusion pressure [CCP] after trauma brain injury [TBI] in ovarectomized female [OVX] rats. In this study female rats are divided into five groups. Control group [Intact] sham group and other groups include: vehicle, estrogen group [1mg/kg] and progesterone group [8 mg/kg] which on all groups TBI was induced by Marmarou method. 30 minutes after TBI, drugs were injected i.p. ICP was measured in spinal cord using a standard procedure. CPP was calculated by the mean arterial pressure [MAP] - ICP. Neurologic scores were measured by motor, eye and respiratory reflex. The results showed after TBI, water content was significantly lower in estrogen and progesterone groups [P<0.001] compared with vehicle group. Analysis showed a stable ICP up to 24 hours. The ICP in estrogen and progesterone groups was significantly decreased at 4 and 24 hours as compared to vehicle group [P<0.001in both cases]. The CPP at 24 hours after TBI, significantly increased in estrogen and progesterone groups compared with vehicle [P<0.001]. Also after TBI, neurologic scores was significantly higher in estrogen and progesterone groups as compared with vehicle [at 1 hours P<0.05, and at 24hours P<0.001 for estrogen], [at 1 hours P<0.01 for progesterone]. Our findings indicated an improvement of ICP, CPP and neurologic scores produced by pharmacologic doses of estrogen and progesterone after TBI in OVX rat. These effects may be contribute to neuroprotective effects of these hormones

Effect of mifepristone on steroid receptor expression and biotransformation of oestrogen and progesterone in rat uterus and deciduoma.

BACKGROUND: [corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus. METHODS: Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity. RESULTS: The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone. CONCLUSION: The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.

Progesterone restores stress induced inhibition of estrous behavior in rat.

Exposure to a stressor (mild electrical shocks to foot, five times per episode, at 1800, 1830, 1900 and 1930 hrs of proestrus) coinciding with period of pre-ovulatory progesterone secretion in rats abolished estrous behavior as shown by the absence of lordosis response and a significant increase in rejection quotient compared to controls. These rats did not show spermatozoa in the vaginal smear next day morning in contrast to their presence in controls. On the other hand, rats treated with progesterone (a single injection, 500 microg in 0.1 ml olive oil at 1800 hr of proestrus) prior to exposure to stressor showed normal estrous behavior, as shown by significantly lower rejection quotient than rats exposed to stress alone, lordosis quotient similar to controls and presence of spermatozoa in the vaginal smear next day. The results, albeit indirectly, to the best of our knowledge, first time indicate that stress induced impaired steroidogenesis leads to suppression of estrous behavior.

17 Beta-estradiol and progesterone upregulate cyclooxygenase-2 expression in the human gingival fibroblasts

Gingivitis is associated with 60-75% of all pregnancies and elevated levels of 17beta -estradiol and progesterone is known to increase gingival inflammation and the proinflammatory prostaglandins in the human gingiva. Since cyclooxygenase-2 [COX-2] is an inducible enzyme responsible for the production of prostaglandins at the sites of inflammation, it is plausible to hypothesize that 17beta - estradiol and progesterone could contribute to gingival inflammation by upregulation of COX-2 expression and subsequent prostaglandin formation. To examine this hypothesis, primary cultures of human gingival fibroblasts [HGFs] from either sex were established. The cells were treated with different concentrations [10-5, 10-7, and 10-9 M] of 17beta -estradiol and progesterone, and expression of COX-2 protein was detected immunocytochemically. The growth potential and proliferation of these cells were studied using trypan blue exclusion method and MTT assay. The results show that both 17beta -estradiol and progesterone upregulate COX-2 expression in the HGFs significantly. In addition, progesterone is more effective than 17beta -estradiol to induce COX-2 expression at 10-5M but not at lower concentration [10-9M]. Furthermore, cells prepared from either sex do not show any difference in COX-2 expression following hormone treatment and neither hormones show any changes in proliferation of these cells. In conclusion, the results of this investigation clearly illustrate significant regulatory effects of 17beta -estradiol and progesterone on COX-2 expression in the cultured HGFs. Thus, one possible pathogenetic mechanism of the female sex hormone-associated gingivitis in vivo may be the synthesis of proinflammatory prostaglandins via upregulation of COX-2 expression by gingiva in response to elevated levels of circulating estrogens and progesterone