This study was designed to examine the state of proliferation in the rat
thyrocyte following the administration of
thyroid stimulating hormone (TSH). An
immunohistochemical technique involving the use of a
monoclonal antibody to
statin, a nonproliferation-specific nuclear
antigen, was developed to measure the subpopulation of cells that have ceased to divide. Following the
random assignment of young male
Sprague-Dawley rats into various groups, the rats in the control group received a single
intraperitoneal (i-p) injection of
normal saline, whereas the experimental groups received single i-p injections of TSH at doses of 0.25, 0.50, and 1.0 IU, respectively. All rats were subsequently sacrificed in groups of three at 1, 2, 4, and 24 hours. The
statin antibody label was readily identified within the
follicle cell nucleus. Results revealed a
statistically significant transient decrease in the
mean percent statin-positive nuclei in the TSH-treated groups. The time- and dose-dependent effect of TSH was maximal at 2 hours and no longer discernible at 24 hours. A second experiment involving the chronic administration of TSH (i-p 0.25 IU twice daily) resulted in a cumulative response with a
statistically significant progressive decrease in the
mean percent of statin-positive nuclei at 5 and 10 days, returning to near normal values 5 days following the cessation of treatment. Determination of the nuclear
optical density of the
statin reaction product by image analysis techniques revealed that a single injection of TSH resulted in a rapid disappearance of the
statin nuclear protein. This result suggests that the disappearance of
statin in the nucleus appears to reflect the event of cells leaving the nondividing quiescent state to resume the
cell cycle traverse following the administration of TSH. The disappearance of
statin appears as an early nuclear event that parallels the earliest known
cytoplasmic pinocytotic response to TSH in the rat
thyroid follicle cell.
