Control of puberty in female rats: the effect of PTU-induced hypothyroidism and systematic undernutrition

Abstract

Sprague-Dawley rats were fed Purina Lab Chow with or without propylthiouracil (PTU), 0.001%, 0.01% or 0.1% PTU, ad libitum from weaning to vaginal opening. Mean values for all pubertal measurements are included in Tables 1 and 2. Growth rate (mean +/- S.E.) was significantly reduced (Neuman-Keuls test; P less than 0.05 level) in all PTU-fed rats (controls 4.9 +/- 0.1 g/day, 0.001% PTU 4.2 +/- 0.2 g/day, 0.01% PTU 3.4 +/- 0.2 g/day, 0.1% PTU 2.5 +/- 0.1 g/day), while age at vaginal opening in rats fed 0.001% PTU (35.8 +/- 0.6 days) or 0.01% PTU (36.1 +/- 0.9 days) was not significantly different from controls (36.0 +/- 0.6 days). Nevertheless, body weight at vaginal opening was lower in rats fed 0.1% PTU (87.6 +/- 4.7 g) than in controls (113.6 +/- 3.7 g). Pubertal body weight of rats fed 0.1% PTU was also reduced (88.6 +/- 3.7 g) but vaginal opening delayed (40.4 +/- 0.8 days). Proportions of body fat (6.1 - 5.1%), protein (15.0 - 14.1%), and water (72.4 - 71.3%) at vaginal opening were the same in control and PTU groups. Serum T4 was greatly diminished and similar in all 3 PTU groups, 0.2 - 0.3 microgram/100 ml, vs 4.8 +/- 0.2 microgram/100 ml in controls; in rats fed 0.1% and 0.01% PTU, T3 was 0.9 +/- 0.4 ng/100 ml and 0.9 +/- 0.6 ng/100 ml, respectively vs 72.6 +/- 5.6 ng/100 ml in controls, but not significantly reduced in the 0.001% PTU-fed group (60.7 +/- 7.9 ng/100 ml). In a second experiment, a group of weanling rats (pair-fed) was selected in which each member was fed the daily amount of control diet eaten by a corresponding age- and weight-matched 0.01% PTU-fed rat. During the experiment, both groups maintained the same body weight, growth rate, and food intake, however, only 45% (n = 11) of the pair-fed animals had vaginal opening by the time their 0.01% PTU-fed counterparts attained first estrus. Although one of the pair-fed (undernourished) rats attained first estrus, no eggs were found. Despite greatly reduced body weight (105.3 +/- 3.5 g vs controls 127.5 +/- 6.6 g), growth rate (3.5 +/- 0.2 g/day vs controls 5.5 +/- 0.1 g/day) and food intake (13.9 +/- 0.7 g/100g BWt/day vs controls 10.1 +/- 0.3 g/100g BWt/day), the 0.01% PTU-fed rats exhibited vaginal opening (36.9 +/- 0.8 days vs controls 35.6 +/- 1 days) and first estrus (39.6 +/- 0.9 days vs controls 36.4 +/- 1 days) at the usual age. In contrast, pair-fed rats had a lower % fat (4.5 +/- 0.1% vs PTU 6.8 +/- 0.4%) and higher % protein (16.5 +/- 0.3% vs PTU 14.3 +/- 0.3%) at the age when 0.01% PTU-fed rats attained first estrus. Serum prolactin levels at first estrus did not differ in rats fed control diet (26.5 +/- 12.4 ng/ml) or 0.01% PTU (8.8 +/- 1.9 ng/ml), or in pair-fed animals (8.8 +/- 4.5 ng/ml) at the age when PTU-fed rats reached first estrus.