ABSTRACT
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.
Subject(s)
Humans , Female , Hormone Antagonists/pharmacology , Hormone Antagonists/therapeutic use , Progesterone/pharmacology , Receptors, Progesterone/agonists , Receptors, Progesterone/antagonists & inhibitors , Receptors, Progesterone/metabolismABSTRACT
Los receptores esteroidales sexuales del tracto genital de la hembra tienen importancia ya que a través de ellos actúan las hormonas responsables de su desarrollo y de sus cambios morfofuncionales. Dado que en su mecanismo de control uno de los factores a tenerse en cuenta son las posibles diferencias entre las distintas especies, los objetivos de nuestro estudio fueron comparar en dos especies distintas la ovina (O) (n=6) y la canina (P) (n=6) la presencia de receptores de estrógenos (RE), progesterona (RP) y de CBG en ovario, tuba uterina y útero de hembras prepúberes (O:n=3; P:n=·3) y adultas (O:n=3; P:n=3). Se realizaron tinción con H-E e inmunocitoquimica según técnica de Stenberger. Los resultados revelaron: en ambas especies en animales durante el ciclo estral inmunorreactividad (IR) positiva marcada para estrógenos en útero, oviducto y ovario siendo comparativamente los RE más numerosos en oviducto de perra que en oveja. En ambos animales en anestro, la IR para RE fue negativa o leve en útero, no evidenciándose su presencia en otros órganos. Los RP variaron según el estadio del ciclo, no mostrando diferencias destacables entre las especies. En las hembras prepúberes de oveja fueron detectados RE Y RP, mientras que en perras éstos no fueron evidenciados. La CBG mostró IR positiva en el tracto de ambos animales durante el ciclo y fue negativa en prepúberes para ambas especies. Se concluye que existen diferencias, especialmente en hembras prepúberes, donde la presencia de RE y RP es detectable en ovejas no así en perras, siendo además, la presencia de RE comparativamente más marcada en tuba uterina de perra en ciclo que en oveja en el mismo estadio.
The sexual steroid receptors of the genital tract of the female has importance since on them the hormones responsible for their development and morphofuncional changes act. Due that in their control mechanism one of the factors to be kept in mind is the possible differences among the diverse species. The objective of our study was to compare in two different species sheep (O) ( n=6) and canine (P) ( n=6) the presence of receptors of estrogens (RE), progesterone (RP) and the presence of CBG in ovary, oviduct and uterus of female prepúberes (O:n=3; Pn=·3) and mature: (O:n=3; Pn=·3) We use H-E tint and and inmunocito chemistry according to technique of Stenberger. The results revealed: in both species of animals during the estral cycle: Inmunorreactivity (RI) positive marked for estrogens in uterus, oviduct and ovary being comparatively much more numerous RE in dog oviduct that in sheep. In both animals in anestro RE was negative or light in uterus, without evidenced of their presence in other organs. The RP varied according to the stage of the cycle not showing remarkables differences among the species. In the prepuber female sheep RE and RP were detected while in dogs they were not evidenced. The CBG showed positivity in the tract of both animals during the cycle and it was negative in both prepuber species We concludes that differences exist especially in prepuber female where the presence of RE and RP are detectable in sheep and no detectable in dogs, being further the comparatively presence of RE in dog oviduct in cycle more marked that in sheep in the same stage.