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At least 109 records · Page 6Linked to original sources
PubMed2005

The role of CBP/p300 interactions and Pit-1 dimerization in the pathophysiological mechanism of combined pituitary hormone deficiency.

CONTEXT: Combined pituitary hormone deficiency (CPHD) in humans is caused by mutations of pituitary-specific transcription factors such as Pit-1. Although many patients with CPHD have an autosomal recessive disorder caused by a Pit-1 DNA-binding mutation, there are a number of reports of mutant Pit-1 molecules that either by prediction or through experimentation bind normally to DNA. OBJECTIVE: The objective of this study was to understand the pathophysiological mechanisms of mutant Pit-1 molecules with intact DNA binding. DESIGN: DNA-binding and functional studies were used to assess five Pit-1 mutations: F135C, R143Q, A158P, K216E, and R271W. RESULTS: In gel-shift studies using well-characterized DNA-binding elements from the GH and prolactin genes, the K126E mutant displayed markedly enhanced Pit-1 dimer binding to either element, whereas the R271W mutant bound with high avidity, but only as a monomer. In contrast, the R143Q mutant was unable to bind these elements, and the F135C and A158P mutants displayed near-normal DNA-binding characteristics. We observed that CBP/p300 bound poorly to the A158P and K216E mutant Pit-1 molecules, but bound normally to the F135C, R143Q, and R271W mutants. In functional assays, CBP/p300 cotransfection with mutant Pit-1 expression vectors resulted in less transactivation of either the GH or prolactin reporter genes. CONCLUSIONS: From these studies, we suggest that CBP/p300 recruitment and Pit-1 dimerization are necessary for Pit-1 target gene activation and are important in the pathogenesis of CPHD.

Base Sequence↗
PubMed1978

Antigenic activity and mobility of bovine pituitary hormones.

The antigenic activity and mobility of bovine pituitary hormones; follicle stimulating hormone (FSH), growth hormone (GH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and melanophore stimulating hormone (MSH) were studied with the aid of agar gel diffusion and electrophoresis. MSH and ACTH were the only hormones not demonstrating antigenicity. Tests by electrophoresis showed "gamma" mobility of the pituitary hormones exhibiting antigenic activity. The observation of antigenic determinants exhibiting identity with immunoglobulins suggests that the bovine pituitary gland houses immunoglobulin molecule and the various pituitary hormones.

Adrenocorticotropic Hormone↗
PubMed1996

Characteristics of the pituitary gland in elderly subjects from magnetic resonance images: relationship to pituitary hormone secretion.

OBJECTIVE: Physiological changes in the pituitary gland with age have not been fully evaluated. The aim of this study was to clarify the morphological characteristics of the pituitary gland by magnetic resonance imaging(MRI) in elderly subjects and to relate them to pituitary hormone secretion. DESIGN AND PATIENTS: We investigated the pituitary MRI in 59 elderly (15 males, 44 females; median 82 years) and 41 young (13 males, 28 females; median 34 years) healthy subjects. RESULTS: Pituitary height, width and volume in the elderly subjects were less than those in the young subjects. Empty sella was more frequently observed in the elderly subjects (19%), especially women, than in the young ones. However, no relation was observed between the pituitary size or volume and basal levels of anterior pituitary hormones. Posterior pituitary bright signal(PBS) on T1-weighted MRI, which is thought to reflect its storage of the neurophysin-peptide complex, was not detected in 29% of the elderly subjects while it could be detected in all the young subjects. None of the elderly subjects showed clinical signs or symptoms of diabetes insipidus. Fasting plasma osmolarity and AVP in the elderly subjects were significantly higher than in the young subjects. Moreover, plasma AVP was significantly higher in the elderly subjects without the PBS than in those with the PBS. CONCLUSIONS: It is suggested that the excessive release of AVP from the posterior pituitary as a result of persistently raised plasma osmolality in the elderly subjects may lead to depletion of the neurosecretory granules in the posterior pituitary gland and may result in disappearance of the posterior pituitary bright signal on T1-weighted MRI. As these morphological changes might relate to the normal physiological occurrence of ageing, we should be cautious in evaluating MRI of the pituitary gland in elderly subjects.

Adrenocorticotropic Hormone↗