Thyroid Hormone Signalling Genes Are Regulated by Photoperiod in the Hypothalamus of F344 Rats

Seasonal animals adapt their physiology and behaviour in anticipation of climate change to optimise survival of their offspring. Intra-hypothalamic thyroid hormone signalling plays an important role in seasonal responses in mammals and birds. In the F344 rat, photoperiod stimulates profound changes in food intake, body weight and reproductive status. Previous investigations of the F344 rat have suggested a role for thyroid hormone metabolism, but have only considered Dio2 expression, which was elevated in long day photoperiods. Microarray analysis was used to identify time-dependent changes in photoperiod responsive genes, which may underlie the photoperiod-dependent phenotypes of the juvenile F344 rat. The most significant changes are those related to thyroid hormone metabolism and transport. Using photoperiod manipulations and melatonin injections into long day photoperiod (LD) rats to mimic short day (SD), we show photoinduction and photosuppression gene expression profiles and melatonin responsiveness of genes by in situ hybridization; TSHβ, CGA, Dio2 and Oatp1c1 genes were all elevated in LD whilst in SD, Dio3 and MCT-8 mRNA were increased. NPY was elevated in SD whilst GALP increased in LD. The photoinduction and photosuppression profiles for GALP were compared to that of GHRH with GALP expression following GHRH temporally. We also reveal gene sets involved in photoperiodic responses, including retinoic acid and Wnt/ß-catenin signalling. This study extends our knowledge of hypothalamic regulation by photoperiod, by revealing large temporal changes in expression of thyroid hormone signalling genes following photoperiod switch. Surprisingly, large changes in hypothalamic thyroid hormone levels or TRH expression were not detected. Expression of NPY and GALP, two genes known to regulate GHRH, were also changed by photoperiod. Whether these genes could provide links between thyroid hormone signalling and the regulation of the growth axis remains to be investigated

Vasoactive intestinal peptide in the anterior pituitary is increased in hypothyroidism

Vasoactive intestinal peptide (VIP) and PRL have been reported to be colocalized in rat lactotropes. To determine whether induced hypothyroidism, known to reduce pituitary PRL concentration, also reduces pituitary concentration of VIP, rats were treated with antithyroid drugs for 3 weeks. Pituitary PRL concentration in male rats (μg/mg protein) was markedly reduced by this treatment (9.3 ± 1.0 vs. 2.3 ± 0.4 when extracted at pH 1.1, 17.9 ± 3.0 vs. 3.4 ± 0.4 when extracted at pH 7.4, 21.8 ± 3.3 vs. 6.7 ± 1.3 when extracted at pH 10.0). Contrary to expectation, pituitary VIP concentration was markedly increased in hypothyroidism; in males from 169.5 ± 20.3 to 834.0 ± 82.2 pg/mg protein, and in females (whose pituitary PRL had been similarly reduced) from 103.1/I ± 34 to 771.6 ± 100.9 pg/mg protein. Serum PRL was significantly reduced in hypothyroid males (7.4 ± 1.6 vs. 28.9 ± 12.2 ng/ml) whereas in females, serum PRL was not significantly altered (41.4 ± 11.6 vs 38.8 ± 14.3 ng/ml). The effect of hypothyroidism was reversed by administration of T 4 in physiological doses. The authenticity of pituitary immunoreactive VIP was further established by demonstrating chromatographic patterns by Sephadex G-50 gel exclusion and reverse phase HPLC separations identical to synthetic VIP. Immunohistochemically reactive VIP cells could not be demonstrated in normal pituitaries, but the marked increase in VIP in hypothyroid animals made it possible to visualize a population of VIP immunoreactive stellate cells which appear to be distinct from hypothyroid lactotropes and thyrotropes.link_to_subscribed_fulltex

Thyroid hormone regulates vasoactive intestinal peptide (VIP) mRNA levels in the rat anterior pituitary gland

Vasoactive intestinal peptide (VIP) is a secretagogue for pituitary prolactin, but the importance of this peptide in the normal control of prolactin secretion is unclear. Recent studies suggest VIP synthesis within the rat anterior pituitary. We have shown (Endocrinology 124:1077) that the content of rat pituitary VIP increases in hypothyroidism. To confirm in situ pituitary synthesis of VIP and determine whether thyroid hormone effects on pituitary VIP relate to changes in VIP mRNA, Northern and in situ hybridization analyses of VIP mRNA in rat pituitaries were performed. Northern hybridization demonstrated an RNA species from rat pituitary consistent with rat VIP mRNA. Hypothyroidsm increased the content of pituitary VIP mRNA, and replacement with 1-thyroxine prevented this increase. In situ hybridization showed multiple, widely-distributed hybridizing cells in pituitaries from hypothyroid animals. A distinct population of VIP-producing pituitary cells exists which may serve to modulate prolactin secretion in a paracrine or autocrine fashion.link_to_subscribed_fulltex

Costly Enforcement of Voluntary Environmental Agreements

Emissions tax, Enforcement, Self-enforcing agreement, Voluntary agreements, L51, Q58,