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Changes in the hypothalamic-pituitary somatotropic function of infant hypothyroid rats
V De Gennaro Colonna1, G Bertola, C B Coco
1Department of Pharmacology, University of Milan, Italy.
Insights
Infant hypothyroidism in rats affects growth hormone (GH) regulation. While GH-releasing hormone (GHRH) system changes appear later, somatostatin (SS) neurons show less sensitivity to thyroid axis disruption.
Area of Science:
- Endocrinology
- Neuroscience
- Developmental Biology
Background:
- The pituitary-thyroid axis is crucial for development and regulates growth hormone (GH) secretion.
- Hypothyroidism during development can impact neuroendocrine systems controlling GH release.
Purpose of the Study:
- To investigate the effects of developmental hypothyroidism on GH-releasing hormone (GHRH) and somatostatin (SS) neuronal systems.
- To determine the timing and nature of functional changes in these regulatory systems.
Main Methods:
- Rats were made hypothyroid using propylthiouracil from parturition.
- Plasma GH, thyroid-stimulating hormone (TSH), and hypothalamic GHRH/SS levels and mRNA were measured at 14 and 21 days.
- Hypothyroid and age-matched control groups were compared.
Main Results:
- Hypothyroid rats exhibited elevated TSH and decreased GH levels at both ages.
- At 14 days, no differences in hypothalamic GHRH/SS were observed.
- At 21 days, hypothyroid rats showed reduced GHRH content and increased GHRH mRNA, while SS remained unchanged.
Conclusions:
- Functional changes in the GHRH system emerge later than GH secretion deficits in infant hypothyroid rats.
- These GHRH alterations appear dependent on GH deficiency.
- Somatostatin neurons demonstrate lower sensitivity to pituitary-thyroid axis perturbations during development.
Abstract:
The effects of the perturbation of the pituitary-thyroid axis induced during development on the functional activity of the growth hormone (GH) regulatory neuronal systems, GH-releasing hormone (GHRH), and somatostatin (SS) were studied in 14- and 21-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Infant hypothyroid rats, both at 14 and 21 days of life, had elevated plasma thyroid-stimulating hormone levels and decreased pituitary and plasma GH levels. Simultaneous determination of hypothalamic GHRH/SS-like immunoreactivity (LI) and GHRH/SS mRNA levels did not reveal any difference in 14-day-old hypothyroid rats when compared with age-matched controls. In contrast, 21-day-old hypothyroid rats had decreased GHRH-LI content and a striking rise in GHRH mRNA levels, whereas SS-LI content and SS gene expression remained unaltered. These data indicate that in infant hypothyroid rats, changes in the functional activity of the GHRH neuronal system occur later than changes in GH secretion and are probably dependent on the GH deficiency. The functional activity of SS neurons was apparently unaltered in these hypothyroid rats, pointing to a lesser sensitivity of this system to the perturbation of the pituitary-thyroid axis.