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To evaluate the dose-response relationship between thyroxine and tibial growth, 60 male rats age 21 days were rendered hypothyroid by administration of methimazole in the drinking water. Twenty-one days later, the hypothyroid rats were randomly divided into 5 groups which received 0, 2, 8, 32, or 64 μg·kg−1·day−1 of T4 im for 21 days. All animals were sacrificed at age 64 days. Rat tibia were removed for measurement of epiphyseal growth plate width and longitudinal growth rate. Serum T4 and IGF-I levels were determined by RIA. Methimazole therapy significantly decreased serum T4, IGF-I, epiphyseal growth plate width, and longitudinal growth rate compared to controls. Epiphyseal growth plate width gradually increased when T4 was administered at doses from 2 to 32 μg·kg−1·day−1 (271±14, 311±15 and 324±11 μm), and subsequently decreased when T4 was given at a dose of 64 μg·kg−1·day−1 (267±8 μm). A similar profile was observed for longitudinal growth rate and IGF-I. We conclude that rat tibial growth has a biphasic response to exogenous T4 administration, and that the effects of T4 on tibial growth may be mediated through IGF-I secretion.

The influence of thyrocalcitonin (TCT) on the enzymes alkaline phosphatase and inorganic pyrophosphatase in rat bone, kidney and intestine was studied. The rats were injected with TCT every hour for 4 hours. They were divided into groups and were sacrificed 1 h after the first, second, third and fourth injection respectively. The plasma calcium was found to be reduced. Enzyme studies showed that: a) in tibia metaphysis homogenates alkaline phosphatase increased in response to TCT, to 198, 175, 154 and 183 per cent of the non-injected rats after 1, 2, 3, and 4 injections, respectively; inorganic pyrophosphatase was elevated to 356, 209, 221, 425 per cent after the same TCT injections. b) In kidney homogenates alkaline phosphatase was reduced to 75, 53, 79, 68 per cent of the non-injected rats after 1, 2, 3 and four doses, respectively; inorganic pyrophosphatase was reduced to 78, 56, 77 and 71 per cent after the same injections of TCT. c) In the jejunum, alkaline phosphatase was found to be 88.5, 71, 91 and 115 per cent of the untreated rats after 1, 2, 3 and 4 injections, respectively; pyrophosphatase in this tissue was found to be 105, 102, 102 and 113 per cent of the normal under the above conditions. The results indicate: 1. TCT causes increases in alkaline phosphatase and inorganic pyrophosphatase activities in bone. The increase of pyrophosphatase is significantly more marked than the increase of alkaline phosphatase; 2. in kidney tissue, the action of TCT on these two enzymes is slower and their activities are equally reduced; 3. in the jejunum no significant effect of TCT on the activity of these two enzymes was observed.

In 20 intact and 20 parathyroidectomized female Sprague-Dawley rats, holes with a diameter of 1.8 mm were bored into the proximal third of the tibia. Half the animals served as controls and received the vehicle, the remainder received daily subcutaneous injections of 100 MRCmU calcitonin in 5 % gelatin. Tetracycline labelling was performed weekly. 5 animals from each group were sacrificed after 3 weeks, the other 5 after 6 weeks. Nondecalcified ground sections through the center of the holes were evaluated with an integration ocular; the surface of the newly formed bone was compared with the original size of the defect. The course of the regeneration for the control animals was in agreement with previous data in the literature. Calcitonin treatment produced a distinct acceleration of the healing process. Presumably, the hormone does not only act via inhibition of bone resorption, but also by stimulating the activity of osteoblasts and by increasing the mineralization of the osteoid seams.