Endocrine Abstracts

The generation of a knockout mouse lacking all POMC-derived peptides by Yaswen et al provided further support for the importance of the melanocortin system in regulating body weight. POMC-null mice have a greater food intake than wild-type littermates on both low fat and high fat diets, resulting in increased body weight. In addition to obesity, these mice have altered pigmentation and defective adrenal development.
The hypothalamo-pituitary-thyroid axis (HPT) in the POMC-null mouse has not been investigated previously. We hypothesised that the POMC-null mouse may have abnormalities of the HPT axis which may contribute to its increased body weight. POMC-null mice and both their heterozygous and wild-type litter mates were killed (aged 13 to 15 weeks), blood collected and peptides extracted from dissected hypothalami. Plasma free tri-iodothyronine (fT3)and total thyroxine (TT4), and hypothalamic alpha melanocyte stimulating hormone (alpha-MSH) and thyrotropin releasing hormone (TRH), were measured using radioimmunassay. Plasma fT3 was markedly elevated in mutant mice compared to wild-type litter-mates (5.2 plus/minus 0.4 [mutant] vs. 3.1 plus/minus 0.2 picomoles per litre [wild type], P<0.005 n = 4 to 8). There was no difference in plasma fT3 between heterozygotes and wild-type controls. Plasma TT4 was similar in all three genotypes.
Since POMC-null mice lack all POMC-derived peptides, hypothalamic alpha-MSH was markedly reduced in these mice (1.2 plus/minus 0.2 [mutant] vs. 10.0 plus/minus 2.8 femtomoles per microgramme protein [wild-type], n = 8 to 12, P<0.005). TRH content in POMC mutant mice was significantly reduced compared to wild-type controls (39.3 plus/minus 6.3 [mutant] vs. 81.4 plus/minus 18.2 femtomoles per microgramme protein [wild-type], P<0.05, n = 7 to 10). Hypothalamic TRH content in heterozygote mice was unchanged compared to wild-type mice.
In conclusion, the POMC-null mouse has an elevated plasma fT3 and reduced hypothalamic TRH content which may be explained by primary hyperthyroidism or alternatively, resistance to thyroid hormones.