Effect of Hypothyroidism and Thyroxine Replacement on Growth Hormone in the Rat*

Coiro, V.; Braverman, Lewis E.; Christianson, Dana; Fang, Shiuh-Bin; Goodman, Maurice H.

doi:10.1210/endo-105-3-641

Cited by 106 publications

(46 citation statements)

References 19 publications

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“…The cause for the paradoxical GH response in hypothyroidism is not known. It might be an expression of a regulatory reaction to the hyperactivity of the GH system characteristic of this state (14)(15)(16). According to this concept, restoring the GH pituitary reserve and normalizing the production of somatomedins abolishes the paradoxical response to TRH.…”

Section: Resultsmentioning

confidence: 99%

Thyroid-Stimulating Hormone, Prolactin, and Growth Hormone Response to Thyrotropin-Releasing Hormone in Treated Children with Congenital Hypothyroidism

et al. 1985

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ABSTRACT. The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with Lthyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH ip conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH. (Pediatr Res 19: 1037-1039,1985 Abbreviations GH, growth hormone PRL, prolactin T3, triiodothyronine T4, L-thyroxine TRH, thyrotropin releasing hormone TSH, thyroid stimulating hormone CH, congenital hypothyroidism tary regulation are well known in hypothyroid patients. Two examples of these alterations are the increased PRL response to TRH (1, 2) and the stimulation of GH secretion by TRH in hypothyroid children (3) and adults (4); these responses do not occur in normal subjects (5). It has been shown that many children suffering from congenital hypothyroidism manifest high serum TSH concentrations for prolonged periods despite adequate replacement therapy, clinical euthyrodism, and normal serum levels of thyroid hormones (7-10). It was suggested that this is due to an elevated threshold for thyrotroph cell TSH suppression by thyroid hormones. The purpose of the present study was to examine both the pituitary-thyroid negative feedback relationship and lactotroph and somatotroph regulation in children with congenital hypothyroidism. MATERIALS AND METHODSTRH tests were performed in 19 children. Group A consisted of 12 congenitally hypothyroid patients aged 1.6 to 9.3 yr attending our clinic for congenital hypothyroidism. All were diagnosed by neonatal thyroid screening during the first weeks of life, and all were treated from the time of diagnosis with T4 and followed by one of us (J.S.). Serum...

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Section: Resultsmentioning

confidence: 99%

Thyroid-Stimulating Hormone, Prolactin, and Growth Hormone Response to Thyrotropin-Releasing Hormone in Treated Children with Congenital Hypothyroidism

et al. 1985

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“…Administration of T 4 by bolus injection has been the preferred method for thyroid rehabilitation in studies on the regulation of the IGF/IGFBP system in hypothyroid animals (Coiro et al 1979, Näntö-Salonen et al 1991. 1·5 g/100 g b.w.…”

Section: Influence Of T 4 Dose and Methods Of Administrationmentioning

confidence: 99%

“…Since all the above studies were carried out in hypothyroid animals, only the study of rehabilitation of neonatal and adult thyroidectomized rats with thyroid hormone could provide new evidence to further understand the regulation of the IGF system by the thyroid hormones. At present, all the studies dealing with thyroid rehabilitation have been carried out by the injection of a single dose of thyroxine (T 4 ) during the neonatal or the adult period separately (Coiro et al 1979, Näntö-Salonen et al 1991, but continuous replacement of thyroid hormone seems more appropriate. In the present study, we investigated the effect of different ways of replacing T 4 in thyroidectomized neonatal and adult rats on the circulating levels and liver mRNA expression of IGFs and their binding proteins IGFBP-1, -2 and -3, as well as on body weight, blood glucose, plasma insulin, thyrotropin (TSH) and GH and pituitary GH content.…”

Section: Introductionmentioning

confidence: 99%

Effect of thyroxine administration on the IGF/IGF binding protein system in neonatal and adult thyroidectomized rats

Ramos

Goya²,

Álvarez³

et al. 2001

Journal of Endocrinology

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The effects of different doses of thyroxine (T 4 ) delivered by injection or s.c. pellet implantation on alterations of the IGF/IGF binding protein (IGFBP) system were studied in neonatal and adult thyroidectomized (Tx) rats. Body weight, blood glucose, plasma insulin, TSH and GH and pituitary GH content, as well as serum IGF-I, IGF-II, IGFBP-1, -2 and -3 and their liver mRNA expression were assayed. Pellet implantation with the smaller dose of T 4 (1·5 µg/100 g body weight (b.w.) per day) in Tx neonatal rats decreased serum IGF-I, -II and the 30 kDa complex of IGFBPs (IGFBP-1 and -2), and increased serum IGFBP-3. Only the larger dose of T 4 (3 µg/100 g b.w. per day) recovered liver mRNA expression of IGF-I and ensured euthyroid status as shown by the normalized levels of plasma TSH. The rapid increase of body weight and serum GH after T 4 administration indicated a high sensitivity to T 4 during the neonatal period. Serum and liver mRNA expression of IGFs and plasma insulin and GH recovered in adult Tx rats after pellet implantation of 1·75 µg/100 g b.w. per day throughout 10 days. The continuous replacement of T 4 by pellet seems to be the most suitable method for thyroid rehabilitation. A very good correlation was found between insulin and IGF-II in Tx neonates treated with T 4 but not between insulin and IGF-I in Tx adults. IGFBP-2 seems to be up-regulated by T 4 deprivation in neonatal and adult rats. Finally, a good correlation as well as a partial correlation were found between IGFs and thyroid hormones in both neonatal and adult Tx populations, suggesting a direct effect in vivo of T 4 on the hepatic secretion of IGFs, as previously suggested in vitro.

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“…T 3 has also been shown to inhibit GH release in vitro from fetal pituitary cells (Mulchahey et al 1988) and from pituitary tumor cells of acromegalic patients (Adams et al 1981). In contrast, in the rat, positive effects of THs on GH secretion have been emphasized in vivo (Peake et al 1973, Coiro et al 1979, Martin et al 1985 and in vitro (Hinkle & Goh 1982).…”

Section: Discussionmentioning

confidence: 99%

Evidence for a negative feedback in the control of eel growth hormone by thyroid hormones

Rousseau¹,

Belle²,

Sbaihi³

et al. 2002

Journal of Endocrinology

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The regulation of growth hormone (GH) by thyroid hormones (THs) has been shown to present species variation. We investigated the regulation of GH in the eel, a representative of an ancient group of teleosts. In vivo administration of triiodothyronine (T 3 ) or thyroxine (T 4 ) significantly reduced pituitary and serum GH levels, as measured by homologous RIA. In order to investigate the ability of THs to regulate GH production directly at the pituitary level, we used a long-term, serum-free primary culture of eel pituitary cells. Both T 3 and T 4 inhibited GH release in a concentration-dependent manner, producing up to 50% inhibition at 10 nM, with an ED 50 of <0·2 nM, within the range of their physiological circulating levels. Other hormones also acting via the nuclear receptor superfamily, such as sex steroids (testosterone, estradiol and progesterone) and corticosteroid (cortisol), had no effect on GH release in vitro, underlining the specificity of the regulatory effect of THs on GH. Measurement of both GH release and cellular content for calculation of GH production in vitro indicated that THs not only inhibited GH release but also GH synthesis. Dot-blot assay of GH messenger RNA (mRNA) using an homologous eel cDNA probe showed a decrease in GH mRNA levels in cells cultured in the presence of T 3 , as compared with control cells. This demonstrated that the inhibition of T 3 on GH synthesis was mediated by a decrease in GH mRNA steady state levels. In conclusion, we demonstrate inhibitory regulation of eel GH synthesis and release by THs, exerted directly at the pituitary level. These data contrast with the rat, where THs are known to have a stimulatory effect and suggest that the pattern observed here in an early vertebrate and also found in birds, reptiles and some mammals including humans, may represent an ancestral and more generalized vertebrate pattern of TH regulation of pituitary GH.

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Effect of Hypothyroidism and Thyroxine Replacement on Growth Hormone in the Rat*

Cited by 106 publications

References 19 publications

Thyroid-Stimulating Hormone, Prolactin, and Growth Hormone Response to Thyrotropin-Releasing Hormone in Treated Children with Congenital Hypothyroidism

Thyroid-Stimulating Hormone, Prolactin, and Growth Hormone Response to Thyrotropin-Releasing Hormone in Treated Children with Congenital Hypothyroidism

Effect of thyroxine administration on the IGF/IGF binding protein system in neonatal and adult thyroidectomized rats

Evidence for a negative feedback in the control of eel growth hormone by thyroid hormones

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