PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11292264

Hypothalamic control of thymic function.

K Hirokawa·M Utsuyama·S Kobayashi
View original source ↗Export metadata ↓

Abstract

Removal of the pituitary gland results in atrophy of the thymus. As the former is under the control of hypothalamus, destruction of anterior portion of the hypothalamus (AHTL) would be expected to negatively influence the thymic function. Contrary to our expectation, however, the thymus became hypertrophic and serum level of growth hormone (GH) markedly increased, when the anterior portion of the hypothalamus was destroyed in rats at 1 month of age and older. The results suggested that AHTL removed the cells secreting GHRIH (growth hormone release inhibitory hormone), but not GHRH (growth hormone releasing hormone), leading to increased pituitary secretion of GH. This high serum level of GH appeared to be responsible for the thymic hyperplasia occurring after AHTL. In other words, the development and aging of the thymus appear to be dependent on the serum level of GH which is under the balance of positive (GHRH) and negative (GHRIH) signals from the hypothalamus. In rats and mice, the serum level of GH is very high just after birth, quickly declines in young adults and does not change greatly thereafter. Thus, it is likely that the initial positive signal is high just after birth and decreasing thereafter with a concomitant increase of negative signal, leading to the onset ofthymic atrophy at around puberty, in association with sex steroid release.

Explore related subjects

Adrenal GlandsAnimalsHumansHypothalamusHypothalamus, AnteriorPituitary GlandRatsThymus GlandJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

K Hirokawa, M Utsuyama, S Kobayashi. 2001. Hypothalamic control of thymic function.. https://pubmed.ncbi.nlm.nih.gov/11292264/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2002

Gender difference in the glucagon response to glucopenic stress in mice.

A gender difference in the glucagon response to insulin-induced hypoglycemia was previously demonstrated in humans. Whether this reflects a gender difference in autonomic activation or in pancreatic alpha-cell regulation is not known. We investigated the glucagon, epinephrine, and norepinephrine responses to neuroglycopenic stress induced by 2-deoxy-D-glucose (2-DG) or insulin in female and male mice. 2-DG increased plasma glucagon levels by 559 +/- 68% in females versus 281 +/- 46% in males (P < 0.01). Plasma levels of epinephrine or norepinephrine after 2-DG administration did not differ between genders. During insulin-induced hypoglycemia, the glucagon response was similarly higher in females (P < 0.001), whereas the plasma catecholamine response was higher in males (P < 0.05). In vivo, the glucagon response to carbachol or clonidine was higher in females (P < 0.05). In isolated islets, the glucagon response to carbachol (100 microM; P = 0.003) but not to clonidine (1 microM) was larger in females. We conclude that in addition to a larger alpha-cell mass (previously described in female mice), an increased sensitivity of the glucagon-producing alpha-cell to cholinergic activation contributes to the larger glucagon response to glucopenic stress in female mice.

Adrenal Glands↗
PubMed2001

Phenotypic spectrum of mutations in DAX-1 and SF-1.

SF-1 (steroidogenic factor-1) (NR5A1) and DAX-1 (dosage-sensitive sex-reversal, adrenal hypoplasia congenital, X chromosome) (NR0B1) are orphan nuclear receptors that are expressed in the adrenal gland, gonads, ventromedial hypothalamus (VMH), and pituitary gonadotrope cells. The function of these genes has been clarified by examining the consequences of naturally occurring mutations in humans, as well as targeted disruption of the genes in mice. Mutations in DAX1 cause adrenal hypoplasia congenita (AHC), an X-linked disorder characterized by adrenal insufficiency and failure to undergo puberty because of hypogonadotropic hypogonadism. Most DAX1 mutations introduce frameshifts and/or cause premature termination of the protein. Relatively few missense mutations have been described and all are located within the carboxy-terminal half of the protein. Transfection assays demonstrate that AHC-associated DAX1 mutations abrogate its ability to act as a transcriptional repressor of SF-1. Most boys affected with AHC present with adrenal insufficiency in early infancy, although a significant fraction present in later childhood or even as young adults. The degree of gonadotropin deficiency is also variable. With the exception of one mild missense DAX1 mutation, genotype-phenotype correlations have been elusive, suggesting an important role for modifier genes. Targeted mutagenesis of Dax1 (Ahch) in mice reveals an additional role in testis development and spermatogenesis. Similar abnormalities appear to be present in humans. Targeted mutagenesis of Sf1 (FtzF1) prevents gonadal and adrenal development, and causes male-to-female sex-reversal. A human XY individual with a heterozygous SF1 mutation presented with adrenal insufficiency and complete sex-reversal; this DNA-binding domain mutation prevents SF-1 stimulation of its target genes. In addition to their clinical relevance, studies of SF1 and DAX1 are proving useful for unraveling the genetic pathways that govern adrenal and gonadal development.

Adrenal Glands↗
PubMed2001

Multiple signals regulate trafficking of the mannose 6-phosphate-uncovering enzyme.

The "uncovering enzyme," which catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal enzyme oligosaccharides, resides primarily in the trans-Golgi network and cycles between this compartment and the plasma membrane. An analysis of green fluorescent protein-uncovering enzyme chimeras revealed that the transmembrane segment and the first 11 residues of the 41-residue-cytoplasmic tail are sufficient for retention in the trans-Golgi network. The next eight residues ((486)YAYHPLQE(493)) facilitate exit from this compartment. Kinetic studies demonstrated that the (488)YHPL(491) sequence also mediates rapid internalization at the plasma membrane. This motif binds adaptor protein-2 in glutathione S-transferase-uncovering enzyme-cytoplasmic tail pull-down assays, indicating that the uncovering enzyme is endocytosed via clathrin-coated vesicles. Consistent with this finding, endogenous uncovering enzyme was detected in purified clathrin-coated vesicles. The enzyme with a Y486A mutation is internalized normally but accumulates on the cell surface because of increased recycling to the plasma membrane. This residue is required for efficient return of the enzyme from endosomes to the trans-Golgi network. These findings indicate that the YAYHPLQE motif is recognized at several sorting sites, including the trans-Golgi network, the plasma membrane, and the endosome.

Adrenal Glands↗