Growth hormone response to clonidine in adversely reared young adult primates: relationship to serial cerebrospinal fluid corticotropin-releasing factor concentrations.
A reduction of the growth hormone (GH) response to the alpha(2) adrenergic agonist clonidine is a neuroendocrine abnormality observed with reasonable consistency among human patients with mood and anxiety disorders. In previous primate studies, in comparison to predictably reared controls, monkeys exposed as infants to maternal variable foraging demand (VFD) rearing exhibited persistent elevations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), as well as other biological disturbances. As CRF has been demonstrated to inhibit GH release, the authors hypothesized that within VFD-reared subjects, animals with relatively high CRF concentrations would exhibit relatively diminished GH responses to clonidine. The current study examined the relationship between the GH response to clonidine in VFD-reared adult primates in relation to a range of both juvenile and follow-up CSF CRF concentrations. Nine bonnet macaques (Macaca radiata) were given ascending dosages of clonidine under ketamine anesthesia. Plasma samples for GH-like immunoreactivity were obtained throughout the session. A significant positive correlation was noted between juvenile CSF CRF concentrations and the levels of the neuropeptide observed in young adults. The mean of the serial CSF CRF concentrations exhibited a significant inverse relationship towards the GH response to clonidine in young adulthood, with relatively high CSF CRF associated with relatively attenuated GH responses to clonidine. These data raise the possibility that a reduced GH response to clonidine may inversely reflect trait-like increases of central nervous system (CNS) CRF activity.
Coplan
J D
JD
Department of Psychiatry, Columbia University College of Physicians & Surgeons, 1051 Riverside Drive, Unit 14, New York, NY 10032, USA. jc45@columbia.edu
Smith
E L
EL
Trost
R C
RC
Scharf
B A
BA
Altemus
M
M
Bjornson
L
L
Owens
M J
MJ
Gorman
J M
JM
Nemeroff
C B
CB
Rosenblum
L A
LA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid*; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors*; D008255:Macaca radiata; D008297:Male
D000316:Adrenergic alpha-Agonists; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D003000:Clonidine