title: Effects of changes in neonatal thyroid status on the development of neuropeptide systems in the rat brain.
abstract: The effects of neonatal thyroid deficiency or hyperthyroidism on the development of neurones containing certain neuropeptides was examined in the brains of rats killed at two weeks of age. Five brain areas were dissected and extracted for radioimmunoassay measurement of vasoactive intestinal polypeptide (VIP), somatostatin, cholecystokinin octapeptide (CCK), substance P and neurotensin, whilst corresponding immunocytochemical data were obtained from a quantitative morphological analysis of cell bodies in the cingulate cortex. The two methods of analysis did not always agree, but in hypothyroidism both the concentration of VIP and the number of cells containing VIP-like immunoreactivity were significantly decreased in the anterior and posterior cingulate cortex. In contrast to these effects on the late maturing VIP neurones, the earlier developing somatostatin system was relatively unaffected, whilst neuropeptides localized in cortical fibres rather than cell bodies (such as substance P and neurotensin) were found by radioimmunoassay to be elevated. Hyperthyroidism had less marked effects than neonatal thyroidectomy, although the concentration of CCK (but not the number of immunostained cells) was significantly increased in the cingulate cortex. Radioimmunoassay results from three subcortical areas showed a decrease in VIP concentration in the hypothyroid hypothalamus, and in hyperthyroidism significant elevations of VIP in the basal ganglia, somatostatin in the hypothalamus and CCK in the hippocampus. It appears that in the brain areas studied thyroid disorders result in dis-synchronous shifts in the developmental patterns of the different neuropeptides, and that the effects of thyroid hormone on peptides as on other transmitters are critically dependent on the developmental profile of the system in question.
authors.affiliation: MRC Developmental Neurobiology Unit, Institute of Neurology, London WC1N 2NS U.K.
authors.forename: P L
authors.initials: PL
authors.lastname: Woodhams
authors.affiliation: MRC Developmental Neurobiology Unit, Institute of Neurology, London WC1N 2NS U.K.
authors.forename: J
authors.initials: J
authors.lastname: McGovern
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: G P
authors.initials: GP
authors.lastname: McGregor
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: O'Shaughnessey
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: M A
authors.initials: MA
authors.lastname: Blank
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: T H
authors.initials: TH
authors.lastname: Adrian
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
authors.affiliation: Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, U.K.
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
authors.affiliation: MRC Developmental Neurobiology Unit, Institute of Neurology, London WC1N 2NS U.K.
authors.forename: R
authors.initials: R
authors.lastname: Balázs