Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys.
Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.
Resko
J A
JA
Department of Physiology and Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA. reskoj@ohsu.edu
Pereyra-Martinez
A C
AC
Stadelman
H L
HL
Roselli
C E
CE
D000735:Androstenedione / Q000097:blood; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm; D013196:Dihydrotestosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D005246:Feedback; D007032:Hypothalamus, Anterior / Q000737:chemistry; D007033:Hypothalamus, Middle / Q000737:chemistry; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009919:Orchiectomy; D011301:Preoptic Area / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*
D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D007986:Luteinizing Hormone; D001141:Aromatase