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Related Experiment Videos

Transgenic mice with inducible dwarfism.

E Borrelli1, R A Heyman, C Arias

  • 1Gene Expression Laboratory, Howard Hughes Medical Institute, La Jolla, California.

Nature
|June 15, 1989
PubMed
Summary

Growth hormone (GH) and prolactin (Prl) producing pituitary cells originate from a common stem cell. This stem cell persists in adult mice and can regenerate both cell types after targeted cell ablation.

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Area of Science:

  • Endocrinology
  • Developmental Biology
  • Genetics

Background:

  • The pituitary gland is crucial for central nervous system control of body physiology.
  • Understanding the cellular origins and differentiation of pituitary cell types is essential for reproductive and metabolic health.
  • Previous studies lacked definitive methods to trace the lineage and developmental timing of specific pituitary cell populations.

Purpose of the Study:

  • To investigate the developmental origins of growth hormone (GH) and prolactin (Prl) producing cells in the anterior pituitary.
  • To determine if GH and Prl cell differentiation are mitotic or post-mitotic events.
  • To identify the progenitor cell population responsible for generating both somatotropes and lactotropes.

Main Methods:

  • Generation of transgenic mice expressing the herpes virus 1 thymidine kinase (HSV1-TK) gene under the control of either the rat growth hormone or rat prolactin promoter.
  • Utilized the thymidine kinase obliteration (TKO) system, where HSV1-TK expressing cells are selectively killed by the drug FIAU.
  • Histological and anatomical analysis of anterior pituitaries in treated transgenic mice to assess cell populations.

Main Results:

  • Treatment of GH-promoter-HSV1-TK mice with FIAU resulted in dwarfism and a near absence of both somatotropes and lactotropes.
  • Treatment of Prl-promoter-HSV1-TK mice with FIAU did not affect pituitary histology, indicating Prl expression/lactotrope differentiation is post-mitotic.
  • A common GH-expressing stem-somatotrope was identified as the progenitor for both GH and Prl cells, persisting into adulthood and capable of repopulation.

Conclusions:

  • Prolactin expression and lactotrope differentiation are post-mitotic events.
  • Both somatotropes and lactotropes arise from a common, mitotically active progenitor, the stem-somatotrope.
  • The stem-somatotrope is present and functional in adult animals, offering potential for pituitary regeneration.

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