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      Influence of Hypothyroidism Duration on Developmental Changes in the Hypothalamic Factors Implicated in Growth Hormone Secretion in the Male Rat

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          The effects of hypothyroidism duration on several factors implicated in GH secretion control were studied in the male rat at different maturity stages, ranging from the peripuberal period to adulthood. Thyroid ablation was performed on 22-day-old Wistar male rats maintained on a low iodine diet (T group). Age-paired controls (C group) were fed with the same diet, supplemented with potassium iodide. Subgroups of T and C animals (aged 32, 42, 52, 82 and 112 days) were studied 10, 20, 30, 60 and 90 days after surgery. After pentobarbital anesthesia, jugular blood was withdrawn before and 5 min after an intravenous TRH stimulus, for GH assay. Hypothalamic and pituitary tissues were obtained in order to measure GH, immunoreactive somatostatin (IR-SRIF) and growth hormone-releasing factor (IR-GRF). Growth rate and serum testosterone confirmed that C rats reached sexual maturity by day 30 of the study. Mean ± SE serum GH (ng/ml) increased (p < 0.05) in C animals from day 10 (38.5 ± 5) to day 30 (67.4 ± 7.3), with no significant variations thereafter. The same time sequence pattern was observed in pituitary GH concentrations. In T rats, both serum and pituitary GH decreased progressively from day 10 to 90, being significantly lower than in C at all times of the study. No GH response to TRH could be found in C groups. In contrast, GH increased significantly (p < 0.05) in T animals after TRH at days 20 and 30. Hypothalamic IR-SRIF concentrations (ng/mg protein) increased (p < 0.05) to adult levels in C rats between days 10 (15.7 ± 3) and 30 (26.3 ± 2.8), remaining unchanged thereafter. T animals showed the same pattern up to day 60. On day 90, IR-SRIF decreased abruptly in T (9.7 ± 2.9) as compared to both normal peers (30.8 ± 7.2; p < 0.01) and 60-day T rats (24.3 ± 5.1; p < 0.05). Hypothalamic IR-GRF (ng/mg protein) also increased (p < 0.05) between day 10 (2.9 ± 0.3) and 30 (4.3 ± 0.7) in C animals. This puberal rise did not occur in 30-day Trats, whose IR-GRF was lower (2.6 ± 0.3; p < 0.01) than in C. It can thus be concluded that a decrease in pituitary GH availability is not the only factor implicated in the abnormal GH secretion found in hypothyroidism. An enhanced GH response to TRH was found to coexist with a 94% reduction in pituitary GH content on days 20 and 30 of hypothyroidism. In the normal rat, hypothalamic IR-SRIF and IR-GRF content increased to adult values in the puberal period. The influence of hypothyroidism on the hypothalamic IR-SRIF content is closely related to its duration, occurring only in long-term thyroid deprivation. Hypothyroidism also prevents the puberal rise of IR-GRF, but does not affect the concomitant increase of IR-SRIF. The blunting of the puberal rise in IR-GRF occurs despite the normal testosterone increase in hypothyroid rats, suggesting that the diminished concentration of thyroid hormone impairs the testosterone-mediated IR-GRF rise.

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          Author and article information

          S. Karger AG
          07 April 2008
          : 54
          : 4
          : 340-345
          Servicio de Endocrinología, Hospital Ramon y Cajal, Madrid, Spain
          125911 Neuroendocrinology 1991;54:340–345
          © 1991 S. Karger AG, Basel

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          Pages: 6
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