Highlights ► Sensitive and specific measurement of TSH in Xenopus laevis and Xenopus tropicalis . ► Ability to measure intracellular, secreted, and circulating TSH. ► First report for direct ...measurement of circulating TSH in amphibians. ► Purification of X. laevis pituitary TSH.
Highlights ► TSH secretion but not expression is negatively regulated during metamorphosis. ► Pituitary sensitivity to TH negative feedback is dependent on metamorphic stage.
PURPOSE OF REVIEWTo understand how thyroid hormone regulates brain development it is important to identify thyroid hormone-responsive brain genes; determine how regulated expression of these genes ...affects brain cell development, physiology, and function; and determine how these physiologic changes affect brain function. The authors summarize recent studies contributing to the understanding of these processes and discuss important new studies that assess thyroid hormone metabolism in the developing brain.
RECENT FINDINGSSpecific thyroid hormone transporters are expressed in the developing brain. Recent data suggest that regulated expression of these transporters may control brain thyroid hormone influx and efflux. Additional data support a role for deiodinases in controlling local iodothyronine concentrations in the developing brain. A series of recent reports assesses the role of thyroid hormone in oligodendrocyte development and axonal myelination. These data provide a cellular and molecular explanation for the hypomyelination observed in neonates that have developed in a hypothyroid state. The cerebellar Purkinje cell is another well-described target of thyroid hormone in the developing brain. A recent study provides evidence that thyroid hormone acts directly on the Purkinje cell to regulate dendritic arborization. Finally, important new data provide insight regarding the functional effects of thyroid hormone deficiency on neuronal activity.
SUMMARYRecent work has provided exciting new insights regarding the mechanisms controlling thyroid hormone action in the developing brain. It seems likely that regulation of thyroid hormone metabolism and transport during brain development is a critically important mechanism of control. Additionally, important new findings have furthered our understanding of the structural and physiologic effects of thyroid hormone deficiency and excess on brain cell function.
In sex determination, globally acting genes control a spectrum of tissue-specific regulators to coordinate the overall development of an animal into one sex or the other. In mammals, primary sex ...determination initially occurs in the gonad, with the sex of other tissues specified as a secondary event. In insects and nematodes, globally acting regulatory pathways have been elucidated, but the more tissue- and organ-specific downstream effectors of these pathways remain largely unknown. We focus on the control of sexual dimorphism in the C. elegans gonad. We find that the forkhead transcription factor FKH-6 promotes male gonadal cell fates in XO animals. Loss-of-function fkh-6 mutant males have feminized gonads and often develop a vulva. In these mutant males, sex-specific cell divisions and migrations in the early gonad occur in the hermaphrodite mode, and hermaphrodite-specific gonadal markers are expressed. However, sexual transformation is not complete and the male gonad is malformed. By contrast, fkh-6 mutant hermaphrodites exhibit no sign of sex reversal. Most fkh-6 hermaphrodites form a two-armed symmetrical gonad resembling that of the wild type, but differentiation of the spermatheca and uterus is variably abnormal. The function of fkh-6 appears to be restricted to the gonad: fkh-6 mutants have no detectable defects in extra-gonadal tissues, and expression of a rescuing fkh-6 reporter is gonad-specific. Genetic and molecular analyses place fkh-6 downstream of tra-1 , the terminal regulator of the global sex determination pathway, with respect to the first gonadal cell division. We conclude that fkh-6 regulates gonadogenesis in both sexes, but is male specific in establishing sexual dimorphism in the early gonad.
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