inibitori dei recettori androgeni topici

[yanez]

grazie della segnalazione



cmq una cosa non mi è ancora molto chiara

il perchè avvenga la ginecomastia

questa può avvenire pare sia con gli inibitori della alfa reduttasi che con i recettoriali


ma perchè?

nel primo caso (inibitori alfa reduttasi)

a livello periferico viene a mancare l'utilizzazione di testosterone che quindi esce dalla cellula? si dirige nei tessuti adiposi dove viene aromatizzato ..escono estrogeni dalle cellule adipose e si dirigono verso le cellule delle ghiandole mammarie e le attivano tramite i recettori ER ?

nel secondo caso (antiandrogeni recettoriali)

applicati a livello topico tipo fluiridil ..che ho letto che ha dato ginecomastia a molti..

che succede ,vengono assorbiti a livello sistemico e ..? impediscono al testo di legarsi ai recettori AR quindi questo esce dalla cellula essendo meno impiegato?
o tutto si gioca a livello delle ghiandole mammarie?

Gli estrogeni stimolano e gli androgeni fermano la crescita del tessuto mammario.

quindi a livello delle cellule mammarie se i recettori AR vengono bloccati le cellule hanno qualche meccanismo di attivazione che le rende ipertrofiche ..o magari le fa replicare ?

avete link che spieghino questa cosa ?mi interesserebbe capire

 

[yanez]

mi rispondo da solo

allora ho trovato questo testo

http://books.google.com/books?id=FVfzRvaucq8C&lpg=PA1203&ots=xZhRr__8ZT&dq=gynecomastia%20%20androgen%20receptor&pg=PA1195#v=onepage&q&f=false
qui parla di antiandrogeni e dice


Citazione:Other drugs may produce gynecomastia by interfering with androgen production or action ,thus increasing the estrogen/androgen ratio effect at the breast. The antifungal agent ketoconazole is a potent inhibitor of testosterone biosynthesis and can cause gynecomastia.However ,because of its pharmacokinetics,the incidence of gynecomastia is low when the drug is given in a once-a-dy dosage this regimen allows the serum testosterone levels to normalize before each succeding dose.Traditional antiandrogens (cyproterone,flutamide).as well as the H2-blocker cimetidine,appear to cause gynecomastia by blocking androgen receptor at the breast rather than by decresing androgen production; they cause an increased effective estrogen/androgen ratio in the breast tissue.This side effect of cimetidine is most common when high doses are used to treat Zollinger_ellison syndrome and is seen much less frequently with other antiulceral drugs,such as rantidine or omeprazole.The blockade of androgen action at the breast by a commercial insecticide has been implicated in an epidemic of gynecomastia in Haitian immigrants.The aldosterone antagonist spironolactone ,frequetly used as a diuretic ,may block androgen receptor as well as interfere with androgen production,thereby leading to an increased effective estrogen/adnrogen ratio at the breast.here ,too,the breast enlargement is seen most commonly at high dosages,as in the treatment of primary hyperaldosteronism.Finasteride ,wich is used in the treatment of prostate disorders and which inhibits 5-a- reductase and reduces intracellular levels of active androgen (dihydrosterone) in targets issues,has also been associated with gynecomastia.
A wide variety of neurotransmitter agonists,antagonists,or modulators that are used to treat hypertension or pshychiatric disorders have been associated with gynecomastia,but the nature and mechanism of this connection are largely unexplored.Also ,such agents commonly are associated with hyperprolactinemia,which may cause secondary hypogonadism.
An increasingly frequent cause of drug-related gynecomastia is cancer chemotherapeutic agents.Gynecomastia associated with such medications may be increasing in prevalence as their spectrum of use is extended to nonmaligant conditions (e.g.,gynecomastia following methrotrexate treatment of rheumatoid arthirtis.
It has been known for many years that such drugs ,particularly alkylating agents ,are highly toxic to spermatogenic epithelium ,causing primary testicular failure with azzospermia,small testicles ,and high serum LH and FSH levels.Serum testosterone levels ,however,usually are normal or low normal,but in some cases of chemotherapy-related gynecomastia,serum estrogen levels have been elevated.A reasonable,but unproven ,theory is that chemotherapy agents produce compensated Leydig cell failure,with normal or low-normal serum testosterone levels maintained only with the stimulus of high serum LH.This incresed serum LH then causes a relative increase in testicular estrogen output,leading to an increase in the circulating estrogen/adnrogen ratio and then gynecomastia.

http://books.google.com/books?id=FVfzRvaucq8C&lpg=PA1203&ots=xZhRr__8ZT&dq=gynecomastia%20%20androgen%20receptor&pg=PA1203#v=onepage&q&f=false



ma quindi se la ginecomastia è dovuta ad un rapporto (ratio) sbilanciato a livello mammario di estrogeni/androgeni e inibire l'aromatasi crea ipogonadismo


qui spiega perchè gli antiaromatasi abbiano un effetto negativo che porta all'ipogonadismo
vedi
Aromatase inhibitors have also been shown to reverse age-related declines in testosterone, as well as primary hypogonadism.
http://www.ncbi.nlm.nih.gov/pubmed/15001605



..allora perchè non provare ad applicare delle eventuali creme ad uso topico a livello mammario che blocchino solo lì i recettori degli estrognei ER ?

sapete se esista qualcosa del genere?

quadra il discorso? che dite?