Evaluation of thyroid function in neonatal and adult rats: The neglected
endocrine mode of action
M. S. Christian and N. A. Trenton
Argus Research, Division of Charles River Laboratories,
905 Sheehy Drive,
Bldg.A, Horsham, PA 19044, USA
Abstract: Although known to regulate growth and development,
cellular metabolism, the use of oxygen, and basal metabolic rate, thyroid
hormones have been only minimally evaluated in neonatal rodents at critical
times of development. Despite some modulation of metabolic rate by other
hormones, such as testosterone, growth hormone, and norepinephrine,
3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) are
the most important metabolic rate modulators. Endpoints used for thyroid
function assessment in neonatal and adult rats include thyroid-stimulating
hormone (TSH), T3, and T4 levels and histopathology. In rodents, decreased
serum levels of T3 and T4 and increased serum TSH levels, with sustained
release of TSH and resultant follicular cell hypertrophy/hyperplasia,
are typical hormonal and histopathological findings attributable to
compounds altering thyroid function. Hypothyroidism early in the neonatal
period can affect reproductive endpoints in both male and female rats,
with the critical period of exposure being the first two weeks postnatal.
Hypothyroidism has been shown to reduce gonadotrophin levels and delay
pubertal spermatogenesis in male rats and to block gonadotropin-induced
first ovulation in immature female rats by decreasing FSH and luteinizing
hormone (LH) serum concentrations. Inclusion of evaluations of TSH,
T3, and T4 assays in multigeneration and developmental neurotoxicity
protocols may assist in risk assessments.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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