Sexually dimorphic effects of testosterone administration on brain allopregnanolone in gonadectomized rats.
BACKGROUND
Clinical and biological evidences have shown a wide range of neuroactive effects of testosterone administration.


OBJECTIVE
Evaluation of the effects of 2-weeks treatment with testosterone (T), Dihydrotestosterone (DHT), and estradiol valerate (E2V) on brain and serum allopregnanolone (AP) in gonadectomized rats of both sexes.


METHODS
AP levels were measured in frontal and parietal lobe, hippocampus, hypothalamus, anterior pituitary, and in serum.


METHODS
Eight groups of Wistar female and eight groups of Wistar male rats were included. For each sex, one group of fertile and one group of gonadectomized rats were employed as control receiving placebo. The others groups received subcutaneous T at the dose of 10 microg/kg/day and 100 microg/kg/day for female rats, and 1 mg/kg/day and 5 mg/kg/day for male rats, or DHT at the doses of 1 microg/kg/day, 10 microg/kg/day, and 100 microg/kg/day for females, and 0, 1 microg/kg/day, 1 mg/kg/day and 5 mg/kg/day for males, or E2V (0.05 mg/Kg/day).


RESULTS
Ovariectomy (OVX) and orchidectomy (OCX) induced a significant decrease in AP in all brain areas analyzed, as well as in serum. In OVX rats, T replacement, as well as E2V, significantly increased AP content in all brain areas and in plasma. In OCX, T and E2V did not actively result in influencing AP concentration in frontal and parietal lobe, while it produced a significant rise in AP levels in the hippocampus, hypothalamus, anterior pituitary, and serum. Conversely, DHT replacement had no affect on AP levels anywhere or at any administered dose, either in males or in female rats.


CONCLUSIONS
Gender difference and T therapy affect brain AP synthesis/release during the reproductive aging. This effect becomes particularly evident in the brain of ovariectomized animals, where the content of this specific neurosteroid is much more responsive than male animals to testosterone replacement.
Pluchino
Nicola
N
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. nicola.pluchino@med.unipi.it
Ninni
Filippo
F
Casarosa
Elena
E
Lenzi
Elena
E
Begliuomini
Silvia
S
Cela
Vito
V
Luisi
Stefano
S
Freschi
Letizia
L
Merlini
Sara
S
Giannini
Andrea
A
Cubeddu
Alessandra
A
Genazzani
Andrea Riccardo
AR
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000378:metabolism*; D051381:Rats; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone