Effect of tibolone administration on central and peripheral levels of allopregnanolone and beta-endorphin in female rats.
OBJECTIVE
We evaluated the effects of tibolone oral administration on neuroendocrine function by investigating the modulation exerted by tibolone administration on allopregnanolone and central and peripheral beta-endorphin (beta-EP) levels in ovariectomized rats.


METHODS
Female Wistar rats (N = 64) were included: 48 rats were ovariectomized, 8 cycling rats were included as controls, and 8 cycling rats were treated with placebo. The ovariectomized animals were divided into six groups: untreated rats and those that received 14-day oral treatment with either placebo, estradiol valerate (E2V) 0.05 mg/kg/d, or tibolone (0.1, 0.5, or 2 mg/kg/d. beta-EP levels were assessed in the frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary, neurointermediate pituitary, and plasma, whereas allopregnanolone levels were measured in the frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum.


RESULTS
The administration of tibolone (0.5 and 2 mg/kg/d) in ovariectomized rats induces a significant increase of allopregnanolone in the frontal lobe, parietal lobe, hippocampus, hypothalamus, whereas in serum a significant increase of allopregnanolone occurs only with the dose of 2 mg/kg/d, a significant decrease in allopregnanolone levels occurs in the adrenal glands. No changes occurred in the anterior pituitary. Tibolone doses of 0.5 and 2 mg/kg/d induced a significant increase in beta-EP content in the frontal lobe, hypothalamus, and neurointermediate lobe; and, at doses of 2 mg/kg/d, in the parietal lobe, anterior pituitary, and plasma, without changes in the hippocampus. Compared with E2V, 0.5 mg/kg/d tibolone showed a similar effect on allopregnanolone and beta-EP in most brain regions.


CONCLUSIONS
Tibolone administration affects beta-EP and allopregnanolone levels, playing a role as a neuroendocrine modulator.
Genazzani
Andrea R
AR
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Italy. a.genazzani@obgyn.med.unipi.it
Bernardi
Francesca
F
Pluchino
Nicola
N
Giretti
Maria Silvia
MS
Begliuomini
Silvia
S
Casarosa
Elena
E
Luisi
Michele
M
Kloosterboer
Helenius J
HJ
D000311:Adrenal Glands / Q000737:chemistry; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D007031:Hypothalamus / Q000737:chemistry; D009490:Neurosecretory Systems / Q000187:drug effects; D009652:Norpregnenes / Q000008:administration & dosage*; D010052:Ovariectomy; D010296:Parietal Lobe / Q000737:chemistry; D010903:Pituitary Gland, Anterior / Q000737:chemistry; D011280:Pregnanolone / Q000032:analysis* / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000032:analysis* / Q000097:blood
D009652:Norpregnenes; D004958:Estradiol; D001615:beta-Endorphin; D011280:Pregnanolone; C027385:tibolone