THYROID HORMONE EFFECTS ON CELL REGULATION

Project: Research project

Description

We will examine thyroid hormone effects on cell growth in cultured GC
cells, a thyroid hormone-sensitive cell line that produces growth hormone.
The G1 period of cells synchronized in the presence of T3 is 12 to 15 hrs,
whereas in cells synchronized in the absence of T3, the G1 is 35 hrs.
Addition of 0.3 nM T3 to cells synchronized in the absence of T3 decreases
the length of the G1 period from more than 35 to 17 hrs. This effect of T3
is restricted to the first 6 to 8 hrs of the G1 period, is stimulated by a
50-fold greater LT4 concentration, and is prevented by cyclohexamide which
itself does not appear toxic to the cells. Thus, T3 action on shortening
the G1 period and accelerating cell growth is mediated by nuclear T3
receptors and involves the synthesis of new proteins. We will now examine
the role of T3 in the induction of specific proteins and phosphoproteins at
the G1 commitment point. We will also determine whether the increase in
nuclear T3 receptor in S phase is due to a change in nuclear T3 receptor
synthesis or degradation rates. Since growth hormone is specifically
induced by T3 in the GC cell line, we have determined GH production and
secretory rate of the different phases of the cell cycle in relation to
changes in concentration of nuclear T3 receptor and chromatin. Growth
hormone production and synthesis rate measured by immunoprecipitation
increased during S phase in parallel to an increase in nuclear T3
receptor. This is caused by an increase in GH mRNA which is proportional
to the increase in growth hormone synthesis. Finally, we measured the
synthesis rate of GH mRNA and found it to be decreased during the S phase
of the cell cycle. Thus, the increase in mRNA for GH that is observed in
the S phase cells results from synthesis at earlier points of the cell
cycle. (N)
StatusFinished
Effective start/end date12/1/7711/30/93

Funding

  • National Institutes of Health
  • National Institutes of Health: $187,843.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Thyroid Hormone Receptors
Triiodothyronine
Thyroid Hormones
S Phase
Cell Cycle
Messenger RNA
Cytoplasmic and Nuclear Receptors
DNA
Growth
Growth Hormone
Chromatin
Cell Line
Nuclear Matrix
Trans-Activators
Coordination Complexes
Conditioned Culture Medium
Gene Library
Epidermal Growth Factor
Disulfides
Population

ASJC

  • Medicine(all)