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Song Guang Ren, Saul Malozowski, Prosper Sanchez, Donald E. Sweet, D. Lynn Loriaux and Fernando Cassorla

Abstract.

Local injection of hormones into the tibial epiphyseal growth plate offers a possible model to answer whether sex steroids can affect bone growth directly. To answer this question, we injected different doses of testosterone enanthate (4, 40, 120 and 400 μg/100 g of rat weight) once into the tibial epiphyseal growth plate of castrated 35-day-old male rats. The contralateral tibia was injected with sesame oil and served as control. All animals were sacrificed at age 42 days. Tibias were removed for measurement of epiphyseal growth plate width and blood was collected for measurement of serum IGF-I and testosterone. The lower doses of testosterone enanthate (4, 40 and 120 μg/100 g) did not produce any significant change in epiphyseal growth plate width. Testosterone at the largest dose tested (400 μg/100 g) increased epiphyseal growth plate width by about 15% compared to control (p < 0.01). At this dose, serum testosterone was not increased, suggesting that the effect on epiphyseal growth plate width was not due to higher systemic testosterone concentrations. No differences in IGF-I levels were observed among the groups. We conclude that direct administration of testosterone enanthate at a dose of 400 μg/100 g into the rat tibial epiphyseal growth plate can increase epiphyseal growth plate width.

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Song Guang Ren, Ze Huang, Donald E. Sweet, Saul Malozowski and Fernando Cassorla

Abstract

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.