Aldo H. Coleoni

Somatotroph response to periodical IGF-I administration to male rats

Insulin-like growth factor I (IGF-I) downregulates growth hormone (GH) expression in pituitary cell cultures. However, in vivo different results were found depending on the experimental protocol used. We determined the kinetics of changes of pituitary and serum GH concentrations after subcutaneous IGF-I administration (240 microg/100 g body weight) to rats every 12 h for various periods. These parameters were correlated with changes in the somatotroph cell population. A significant increase in serum GH was registered at 6 h after IGF-I injection. At this time, some somatotroph cells exhibited ultrastructurally signs of high secretory activity, whereas adjacent somatotroph cells showed a quiescent appearance with sizeable stores of secretory granules. In contrast, serum GH levels remained unchanged at 1, 2 and 12 h after each IGF-I injection. Pituitary GH concentrations were comparable to control levels during the first 48 h and declined significantly at 72 h and 96 h of IGF-I treatment. After these prolonged periods of time of treatment, the size and extension of organelles involved in protein synthesis decreased and mature secretory granules in the cytoplasm increased significantly in GH-secreting cells. The somatotroph cell density remained unchanged even at 96 h of treatment. In conclusion, our results suggest that periodical IGF-I administration to rats does not inhibit GH secretion. Interestingly, IGF-I injections induced early and significant increases in serum GH levels. This result may be a consequence of a temporary stimulatory action on somatotroph cells concurrent with increased secretory activity.

Monoamine oxidase (MAO) activity and its forms in normal and pathological human thyroid tissues.

Monoamine oxidase (MAO) activity and its forms were measured in normal human thyroid glands (39 samples from necropsy and four from perinodular tissues) and in pathological thyroid glands (13 multinodular goitres, three carcinomas, seven chronic thyroiditis, five Graves’ disease and seven follicular, seven foetal and five embryonal adenomas). MAO activity in carcinomas was lower than in normal perinodular thyroid control tissue; in Graves’ disease, foetal and embryonal adenomas it was significantly higher than in the normal control. The use of clorgyline (a selective MAO A inhibitor) and deprenyl (selective MAO B inhibitor) allowed estimation of the relative proportion of MAO forms. A high proportion of MAO A (more than 90%) was observed, both in normal and in pathological thyroid tissues. Changes in total thyroid MAO activity, but not in its forms, were found in different pathologies of the thyroid gland.

Growth hormone (GH) treatment reduces peripheral thyroid hormone action in girls with Turner syndrome

Objective  Turner syndrome (TS) is an indication for GH therapy in spite of the modest growth response. Somatic growth depends not only on GH insulin‐like growth factor I (IGF‐I) axis but also on thyroid hormone (TH) status. We have previously reported that supraphysiological IGF‐I levels diminished TH actions in rat tissues by reducing the nuclear TH receptor (TR). GH treatment to TS patients induces high IGF‐I levels and therefore a reduction of TH action in tissues may be expected. We aimed at evaluating the effect of GH therapy in TS girls on peripheral TH action.

Differential modulation of liver and pituitary triiodothyronine and 9-cis retinoid acid receptors by insulin-like growth factor I in rats.

Triiodothyronine (T(3)) exerts most of its effects through nuclear thyroid hormone receptors (TRs) that bind mainly as heterodimers with retinoid-X receptors (RXRs) to thyroid hormone response elements in target genes. It is well known that T(3) activates the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in rats. In turn, IGF-I inhibits the T(3)-induced GH production in cell cultures. The impact of IGF-I on T(3) action has only been partially explored. We have presented evidence that IGF-I feeds back to limit specific metabolic actions of T(3) in rat liver through a downregulation of nuclear TR number and its mRNA expression. We have also found that IGF-I injected to rats inhibited pituitary GH production. In this study we aimed at exploring whether the IGF-I-induced feedback loop on T(3)-action in the liver also operates in the pituitary gland. The mechanism of the liver TR mRNA reduction induced by IGF-I was also studied. We evaluated the effect of recombinant human (rh) IGF-I administration (240 microg/100 g of body weight subcutaneously every 12 hours for 48 hours) to adult male Wistar rats on TR and RXR proteins (Western blot) from pituitary, liver, brain, and thyroid and TR mRNA (Northern blot) from pituitary and liver. The transcriptional rate of liver TR gene (run-on assay) was also determined. In pituitary, TR protein and TR mRNA isoforms were reduced by rhIGF-I. No changes in TR proteins in brain and thyroid were observed. Nuclear run-on assay revealed that IGF-I reduced the TR gene transcriptional rate in liver. A significant increase in RXR proteins in liver and pituitary without changes in thyroid and brain was induced by IGF-I. In conclusion, these results indicate that in pituitary, IGF-I downregulates TR expression, similarly as previously found in liver. A reduced transcriptional rate of TR gene is implicated in the IGF-I effect on the liver. The increase in RXR protein levels may be also involved in the expression of T(3) specific actions in liver and pituitary.

Activity of T3–Responsive α–Glycerophosphate Dehydrogenase (α–GPD) and the Characteristics of Nuclear T3–Binding in the Male and Female Rat

The present study explores the possible sex-related difference in the metabolic effects of thyroid hormones by studying the activity of the liver mitochondrial T3–responsive α–glycerophosphate dehydrogenase (α–GPD). In parallel experiments we characterized the liver nuclear T3–receptors in male and female rats. We also attempted to determine whether such differences are related to the different sex-hormone content.

Induction of Liver Mitochondrial α-Glycerophosphate Dehydrogenase (α-GPD) by Glucocorticoid Deficit: Role of the Nuclear T3-Receptor (nT3-R)

It was reported that adrenalectomy in rats induced an increase in mitochondrial α-glycerophosphate dehydrogenase activity (α-GPD) although the mechanism of this activation was not elucidated (1). More recently, we found that the increase in α-GPD activity under a glucocorticoid deficit was accompanied by an increase in the affinity of liver nT3-R (2). This paper explores further the mechanism involved in the activation of α-GPD under a glucocorticoid deficit. We also attempted to establish a relationship between the changes in the affinity of nT3-R and the activity of this T3-dependent enzyme.