Differential responsiveness of the pituitary-thyroid axis to thyrotropin-releasing hormone in mouse lines selected to differ in central nervous system sensitivity to ethanol.
Long-sleep (LS) and short-sleep (SS) mice are genetic lines that differ in central nervous system sensitivity to ethanol. The possible role of TRH in mediating the difference in the thyroid status between these two lines was investigated. An increase in TRH gene expression in the paraventricular nucleus and TRH peptide levels in the hypothalamus between postnatal days 8-14 in both SS and LS mice coincided with increased circulating levels of thyroxine during this critical period of central nervous system development. No significant differences in TRH biosynthesis were observed between LS and SS mice during this time. Exogenous administration of TRH to LS and SS mice on day 8, when endogenous serum thyroxine levels were equivalent, resulted in a greater increase in serum thyroxine in SS mice (150%) than LS mice (51%). The differential response to the TRH stimulation test was also present on day 14 (SS, 43%; LS, 18%). The differential responsiveness of the pituitary-thyroid axis to exogenous TRH paralleled the differential increase in endogenous serum thyroxine observed between day 8 and 14 in these mice. Administration of TRH to day 20 and adult (60 days) LS and SS mice resulted in nearly equivalent (approximately 75%) increases in free thyroxine serum levels, yet the magnitude of thyroxine release was 50% greater in SS mice, due perhaps to between-line differences within the thyroid glands. It is unlikely that dissimilar endogenous levels of TRH account for the intrinsic difference in the thyroid status in LS and SS mice. Instead, the increased pituitary-thyroid responsiveness to TRH in SS mice during the second postnatal week may translate into increased functional capacity of the thyroid gland in adult SS relative to LS mice.
Erickson
J D
JD
Unit on Molecular and Cellular Neurobiology, National Institute of Mental Health/Alcohol, Drug Abuse and Mental Health Administration, Bethesda, Maryland 20892.
Masserano
J M
JM
Zoeller
R T
RT
Eskay
R L
RL
Weiner
N
N
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006651:Histocytochemistry; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009693:Nucleic Acid Hybridization; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000502:physiology*; D011863:Radioimmunoassay; D012890:Sleep / Q000187:drug effects; D013961:Thyroid Gland / Q000378:metabolism / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D013974:Thyroxine / Q000097:blood
D010281:Parathyroid Hormone; D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; D004247:DNA; D013974:Thyroxine