HYPOPITUITARISM: CLINICAL &MOLECULAR CHARACTERIZATION

Project Details

Description

Pituitary development and hormone expression in mammals is controlled by pituitary-specific transcription factors including: Rpx, Lhx3, Prop-1 and Pit-1. These factors initiate a cascade of development events resulting in mature pituitary cell-types and mutation or deletion of the genes encoding these factors have been shown to result in anterior pituitary hormone deficiency in mammals. A consistent feature of these animal models is GH deficiency associated with either TSH and/or prolactin deficiency. Many patients have been described with complete or partial deficiency of hormone secretion from these cell types. However, in many cases, the pituitary function has not been carefully evaluated and patients are frequently diagnosed as having 'idiopathic' GH deficiency. My laboratory and others have described a genetic basis for combined pituitary hormone deficiency (CPHD) in man due to point mutations in the Pit-1 and Prop-1 genes. We and others have also discovered Pit-1 and Prop-1 mutations in patients with presumed idiopathic GH deficiency. These observations demonstrate that mutations in these genes may be a frequent cause of not only CPHD, but also 'isolated' GH deficiency. In addition, mutation or deletion of other pituitary developmental factors (Rpx, also 'isolated' GH deficiency. In addition, mutation or deletion of other pituitary developmental factors (Rpx, Ptx2 and Lhx3) has been associated with pituitary hormone deficiencies. This proposal will clinically characterize patients with hypopituitarism and investigate the structure of candidate genes. Study of mutations in pituitary transcription factors and their diverse pathophysiological mechanisms should increase our understanding of anterior pituitary gland development and gene regulation in normal and disease states. The candidate is an Associate Professor of Pediatrics at Harvard Medical School and an Associate Physician at Children's Hospital, Boston, where she is the director of the reproductive endocrine unit and endocrine clinical laboratories. She has independent support to study GnRH gene expression (RO1-HD34551) and Pit-1 gene function (R01-DK53977) in mammals. She also directs a CRC protocol to evaluate and categorize patients with hypopituitarism. She actively mentors four BE/BC pediatric endocrinologists, a BE obstetrician-gynecologist, two of whom are funded by the intramural Endocrine training grant (T32HD07277), one funded by a mentored grant (K11DK02329), one by a Janeway fellowship award from Children's Hospital mentoring success, in an environment rich with academic opportunities, this award will allow her to increase her mentoring activities and to enhance her own commitment to patient- oriented research.
StatusFinished
Effective start/end date6/1/003/31/05

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $56,976.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $85,720.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $23,760.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $82,349.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $87,481.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $84,009.00

ASJC

  • Genetics

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