title: Growth hormone responses to thyroid hormone in the neonatal rat: resistance and anamnestic response.
abstract: Differences in the growth hormone (GH) responses to primary and to secondary stimulation with triiodothyronine (T3) were studied in rats deprived of thyroid hormone from birth. Neonatal hypothyroidism was induced in pups by feeding pregnant rats an iodine-deficient, propylthiouracil-containing diet. T3 stimulation was carried out in pups by subcutaneous injection of a single dose of 50 mug T3/100 g body wt. Pituitary GH content, rate of GH synthesis in vitro, and GH messenger (m)RNA activity in a cellfree translation system were measured.No significant differences in body weight and in pituitary GH content were observed between hypothyroid and normal pups at ages 1, 3, and 6 d. 10- and 28-d-old hypothyroid pups showed a significant arrest of growth, decreased pituitary GH content, and development of GH responsiveness to T3. In contrast, serum thyroxine concentration in hypothyroid pups was <0.15 mug/dl, significantly lower than normal at all ages.GH synthesis and GH mRNA activity studied in pituitaries of 28-d-old rats were expressed as percent total protein synthesis and percent mRNA activity, respectively. GH synthesis and mRNA activity were 3.0 and 2.6% in hypothyroid rats, 3.3 and 2.9% in hypothyroid rats given a single T3 injection 14 d earlier (T3-withdrawn rats), and 26.8 and 27.1% in normal rats. Administration of T3 to hypothyroid rats induced an increase in GH synthesis and GH mRNA activity, reaching 5.8 and 5.6% 12 h after primary stimulation and 12.2 and 16.1% 12 h after secondary stimulation. The response rates were linear but 2.5-fold more rapid after secondary stimulation. The latter response was similar to that observed after T3 stimulation of rats rendered hypothyroid during adulthood. The responses of GH synthesis and mRNA activity were concordant after both primary and secondary T3 stimulation. A twofold increase in both parameters was observed as early as 2 h after T3 injection. Four conclusions can be drawn from these experiments. First, during neonatal life, GH accumulation in rat pituitaries is independent of thyroid hormone and is insensitive to T3. Second, GH dependence on and sensitivity to thyroid hormone is acquired between the 6th and 10th d of neonatal life. Third, secondary T3 stimulation produces an anamnestic response manifested by an increased rate of GH synthesis and mRNA activity. Fourth, primary T3 stimulation is not associated with a lag in the endogenous translation of the newly accumulated GH mRNA.
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis* / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013974:Thyroxine / Q000097:blood; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D014284:Triiodothyronine; D013006:Growth Hormone; D013974:Thyroxine