Abstract
The 3alpha-hydroxy metabolites of progesterone (P), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone, A-PREG) and 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone, PREG), have been found to be among the most potent ligands of gamma-aminobutyric (GABA)-A receptors; in experimental animals, they have been found to have anxiolytic, hypnotic and anticonvulsant effects. Similar to those of the benzodiazepines and barbiturates that interact with GABA-A receptors. The present study was undertaken to determine plasma A-PREG and PREG concentrations in the luteal phase in women with partial epilepsy, in order to determine if an impaired metabolism of P occurs in this convulsive disorder. We measured plasma P, A-PREG and PREG levels in 15 women with partial epilepsy in the intercritical phase, and in 15 age-matched healthy women, during the luteal phase of the ovarian cycle (22nd-24th day). The mean plasma ± S.E. A-PREG levels (three blood samples) were 0.7±0.6 ng/ml in the epileptic women and 0.5±0.2 ng/ml in controls, with no significant difference between the two groups (p=NS); the PREG levels were also similar (1.4±1 ng/ml and 1±1.1 ng/ml, respectively: p=NS). A significant correlation was found between P levels and both A-PREG and PREG levels (r=0.72, p<0.001 and r=0.79, p<0.001, respectively). There were no significant differences between the two groups in terms of serum adrenocorticotropic hormone, cortisol, dihydroepiandrosterone-sulfate, follicle stimulating hormone, prolactin, luteinizing hormone or estradiol levels.
Sommario
I 3alfa-idrossimetaboliti del P, 3alfa-idrossi-5alfa-pregnan-20-one (allopregnanolone, A-PREG) e 3alfa-idrossi-5beta-pregnan-20-one (pregnanolone, PREG) sono risultati tra i più potenti ligandi dei GABA-A recettori; nell'animale da esperimento essi hanno mostrato infatti di possedere proprietà ansiolitica, ipnotica ed anticonvulsivante sovrapponibile alle benzodiazepine ed ai barbiturici. Questo studio è stato condotto dosando la concentrazione plasmatica di A-PREG e PREG nella fase luteale del ciclo mestruale in 15 pazienti affette da epilessia parziale del lobo temporale in fase intercritica ed in 15 soggetti omogenei per sesso ed età, al fine di evidenziare un eventuale alterato metabolismo del P e dei suoi metaboliti in soggetti con sindrome comiziale.
La concentrazione plasmatica media (sono stati effettuati 3 prelievi ematici) di A-PREG era di 0.7±0.6 ng/ml nelle pazienti e di 0.5±0.2 ng/ml nei controlli, mentre quella di PREG risultava essere rispettivamente 1.4±1 ng/ml e 1±1.1 ng/ml, senza che per nessuno dei due ormoni fosse possibile evidenziare una differenza statisticamente significativa tra pazienti e controlli (p=NS).
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This work was partially supported by grants from the Ministero della Università e della Ricerca Scientifica e Tecnologica (M.U.R.S.T. 40% and 60%).
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Galli, R., Michelini, S., Bartalena, L. et al. Circulating levels of anticonvulsant metabolites of progesterone in women with partial epilepsy in the intercritical phase. Ital J Neuro Sci 17, 277–281 (1996). https://doi.org/10.1007/BF01997786
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DOI: https://doi.org/10.1007/BF01997786