ABSTRACT
The hypothalamic-pituitary-thyroid axis is governed by hypophysiotropic TRH-synthesizing neurons located in the hypothalamic paraventricular nucleus under control of the negative feedback of thyroid hormones. The mechanisms underlying the ontogeny of this phenomenon are poorly understood. We aimed to determine the onset of thyroid hormone-mediated hypothalamic-negative feedback and studied how local hypothalamic metabolism of thyroid hormones could contribute to this process in developing chicken. In situ hybridization revealed that whereas exogenous T4 did not induce a statistically significant inhibition of TRH expression in the paraventricular nucleus at embryonic day (E)19, T4 treatment was effective at 2 days after hatching (P2). In contrast, TRH expression responded to T3 treatment in both age groups. TSHß mRNA expression in the pituitary responded to T4 in a similar age-dependent manner. Type 2 deiodinase (D2) was expressed from E13 in tanycytes of the mediobasal hypothalamus, and its activity increased between E15 and P2 both in the mediobasal hypothalamus and in tanycyte-lacking hypothalamic regions. Nkx2.1 was coexpressed with D2 in E13 and P2 tanycytes and transcription of the cdio2 gene responded to Nkx2.1 in U87 glioma cells, indicating its potential role in the developmental regulation of D2 activity. The T3-degrading D3 enzyme was also detected in tanycytes, but its level was not markedly changed before and after the period of negative feedback acquisition. These findings suggest that increasing the D2-mediated T3 generation during E18-P2 could provide the sufficient local T3 concentration required for the onset of T3-dependent negative feedback in the developing chicken hypothalamus.
Subject(s)
Feedback, Physiological/physiology , Gene Expression Regulation, Developmental/genetics , Hypothalamo-Hypophyseal System/metabolism , Iodide Peroxidase/metabolism , Neurons/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , RNA, Messenger/metabolism , Thyroid Gland/metabolism , Thyrotropin-Releasing Hormone/metabolism , Thyroxine/metabolism , Animals , Brain/drug effects , Brain/embryology , Brain/metabolism , Cell Line, Tumor , Chick Embryo , Ependymoglial Cells/drug effects , Ependymoglial Cells/metabolism , Feedback, Physiological/drug effects , Gene Expression Regulation, Developmental/drug effects , Humans , Hypothalamo-Hypophyseal System/embryology , Hypothalamus/drug effects , Hypothalamus/embryology , Hypothalamus/metabolism , Immunohistochemistry , In Situ Hybridization , Iodide Peroxidase/drug effects , Neurons/drug effects , Nuclear Proteins/drug effects , Nuclear Proteins/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/embryology , Pituitary Gland/drug effects , Pituitary Gland/metabolism , RNA, Messenger/drug effects , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Thyroid Nuclear Factor 1 , Thyrotropin, beta Subunit/genetics , Thyroxine/pharmacology , Transcription Factors/drug effects , Transcription Factors/metabolism , Triiodothyronine/drug effects , Triiodothyronine/metabolism , Iodothyronine Deiodinase Type IIABSTRACT
OBJECTIVES: The primary objective of this study was to perform new, relevant information about cranial suture closure in adults. Single nucleotide polymorphisms (SNPs) in targeted genes were examined, which encode factors that play an important role in cranial suture development and maintenance. Our hypothesis was that some of these genes and polymorphisms can influence the cranial suture obliteration status in adulthood as well. METHODS: Ossification of cranial sutures was ascertained according to Meindl and Lovejoy's vault system (1985: Am J Phys Anthropol 68(1):57-66), and peripheral blood samples were collected during autopsy procedure of 106 individuals at the Department of Forensic and Insurance Medicine, Semmelweis University, Hungary. Genotyping of SNPs was conducted using competitive allele-specific polymerase chain reaction KASPar chemistry. Multivariate linear models were used to test whether SNP polymorphism of the investigated genes has a significant effect on the ectocranial suture synostosis in adults. RESULTS: The msh homeobox 1 (MSX1): rs3821947 polymorphism showed significant association with the extent of suture obliteration. CONCLUSIONS: Cranial suture closure in adults is a complex, multifactorial process. According to previous results MSX1 has a role in calvarial bone development and it has an effect on sutural mesenchyme in latter postnatal stages. Our results demonstrate MSX1 effects on suture obliteration in adulthood. These findings represent new, relevant information indicating that genetic background can have an impact on cranial suture closure in adults.
