title: Dydrogesterone increases allopregnanolone in selected brain areas and in serum of female rats.
abstract: OBJECTIVE
  To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid allopregnanolone and the opioid beta-endorphin.
  
  
  METHODS
  Experimental study on animal model.
  
  
  METHODS
  Academic research environment.
  
  
  METHODS
  72 Wistar female rats.
  
  
  METHODS
  One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day).
  
  
  METHODS
  Allopregnanolone and beta-endorphin, assessed in different brain areas and in circulation.
  
  
  RESULTS
  Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and reduced beta-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of beta-endorphin induced by E2V.
  
  
  CONCLUSIONS
  Dydrogesterone interacts with allopregnanolone levels (less with beta-endorphin), and it can be considered important modulator of the neuroendocrine function.
authors.affiliation: Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pluchino
authors.forename: Elena
authors.initials: E
authors.lastname: Lenzi
authors.forename: Elena
authors.initials: E
authors.lastname: Casarosa
authors.forename: Vito
authors.initials: V
authors.lastname: Cela
authors.forename: Silvia
authors.initials: S
authors.lastname: Begliuomini
authors.forename: Filippo
authors.initials: F
authors.lastname: Ninni
authors.forename: Letizia
authors.initials: L
authors.lastname: Freschi
authors.forename: Stefano
authors.initials: S
authors.lastname: Luisi
authors.forename: Andrea Riccardo
authors.initials: AR
authors.lastname: Genazzani
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004394:Dydrogesterone / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D011280:Pregnanolone / Q000097:blood* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D004958:Estradiol; D001615:beta-Endorphin; D004394:Dydrogesterone; D011280:Pregnanolone