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Pure Appl. Chem., 2003, Vol. 75, No. 11-12, pp. 2055-2068

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.