Control of Puberty in Female Rats: The Effect of PIU-Induced Hypothyroidism and Systematic Undernutrition

Abstract

Summary: 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 puhertal measurements are included in Tables 1 and 2. Growth rate (meant±5.E.) was significantly reduced (Neuman-Keuls test; P<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 (15.0-14.11). 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 μg/100 ml vs 4.8±0.2 μg±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 127.56.6 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-féd rats exhibited vaginal opening (36.920.8 days vs controls 35.621 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±0.34 vs PTU 14.32 0.3%) at the age when 0.01% PTU-fed rats attained first estrus. Serum prolactin levels at first estrus did not differin rats fed control diet (26.5±12.4 ng/ml) or 0.01% PTU (8.8±1.9 ng/ml), or i n pair-fed animals (8.8±4.5 ng/ml) at the age when PTU-fed rats reached first estrus.

Speculation: These data show that despite low food intake and retarded growth, female rats made hypothyroid by feeding them PTU during the post-weaning period under go sexual maturation at the ususal age. This is in contrast with the delayed puberty observed in pair-fed (undernourished) animals that attain the same body weight and growth rate. The proportion of fat/lean tissue in the PTU-fed rats is indistinguishable from that in their pubertal controls, but differs greatly in pair-fed animals at that age.

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