Histomorphometric study of the enhancement of renal compensatory hypertrophy by ACTH in the rat.

In the female adult rat, renal compensatory hypertrophy is greatly enhanced by hyperadrenocorticism elicited by the administration of ACTH given at a dose of 18 Y/100 g BW/d for 7 days after uninephrectomy (UN). This renotrophic effect of ACTH is particularly prominent in rats drinking a NaCl solution (9 g/l). In the present experiments, we performed histomorphometrical measurements of the glomerular tuft (GT) and the proximal tubule (PT) in the hypertrophying kidney (HK) remaining 7 days after UN in 10 rats treated with ACTH and 7 control animals. The histologic preparations were examined under light microscopy with the "Kontron" image analyzer. ACTH increased the weight of the HK (1213.8 +/- 20.3 mg versus 1037.3 +/- 13.3, p less than 0.001) and determined an enlargement of the cross sectional area of the GT (12559 +/- 3351.3 mu2 versus 10486 +/- 407.5, p less than 0.01) and of the epithelial area of the PT (1751 +/- 40.8 mu2 versus 1586 +/- 41.5, p less than 0.025). These morphometrical data are consistent with the increased Protein/DNA ratio - a marker of cellular hypertrophy - found in other rats studied under the same experimental conditions. The increased weight gain of the HK elicited by ACTH is related to the hypertrophy of the epithelial cells of the PT and possibly to an enlargement of the glomeruli.

[Bromocriptine and the growth hormone response to thyroliberin in the insulin-dependent diabetic]. / Bromocriptine et réponse d'hormone de croissance à la thyrolibérine chez le diabétique insulino-dépendant.

The effect of bromocriptine on growth hormone (GH) responses to TRH was studied in 14 insulin-dependent diabetics. The effect of this dopaminomimetic agent was inconstant. In the 6 patients with inadequate responses of GH to TRH, bromocriptine inhibited this response. Inversely, it appeared capable of stimulating a GH response in certain non-responders. The could suggest the existence of disturbances of dopaminergic control of GH secretion in diabetics, but the lack of reproducibility of responses of GH to TRH makes this an uncertain conclusion.

[Modification of the renotrophic action of adrenal hypercorticism by nutritional factors in uninephrectomized rats]. / Modulation de l'effet rénotrophique de l'hypercorticisme surrénalien par des facteurs nutritionnels chez le rat uninéphrectomisé.

In the rat renal compensatory hypertrophy (RCH) was enhanced by hyperadrenocorticism induced by the administration of a long acting ACTH at a dose of 18 Y/100 g body weight/d. for 7 d. after uninephrectomy (UN). In the present experiments we compared the differences delta between the weight, the content in protein, RNA and DNA of the left solitary kidney and the same determinations done on the right kidney excised at UN 7 d. earlier. The rats drank freely a isotonic solution of NaCl (G1) or KCl (G2) or glucose (G3, G4). The rats of group G1, G2 and G3 received a standard solid food; the G4 rats ate a K poor diet. About half of the animals were treated with ACTH. RCH occurred in all the rats even when they lost body weight. The gain in weight of the solitary kidney was enhanced in all the rats treated with ACTH but not in the G2 rats loaded with KCl. This renotropic action of hyperadrenocorticism was most prominent in the K depleted G4 rats. The protein/DNA ratio, a marker of cellular hypertrophy, was increased by hyperadrenocorticism in the G1 and D2 rats drinking respectively the NaCl or the KCl solutions. This ratio did not change in the ACTH treated G3 and G4 rats drinking the glucose solution suggesting that, in this experimental condition, cellular hyperplasia and hypertrophy occurred at the same extent. These experiments suggest that, in the uninephrectomized rat, the renotrophic action of ACTH is modulated by nutritional factors. The enhancement of RCH by ACTH may be related to hyperglycemia, hyperinsulinism or altered handling of Na and K by the nephron.

Enhancement of renal compensatory hypertrophy by hyperadrenocorticism and its modulation by nutritional factors.

Renal compensatory hypertrophy (RCH) is enhanced by ACTH in the uninephrectomized rat. In the present experiments, the kidney weight and its content in protein, RNA and DNA were determined in 48 adult, female rats; 24 had free access to a NaCl solution (9 g/l) and the others to a glucose solution (50 g/l). In each group 12 rats were sacrificed 2 or 7 d. after uninephrectomy (UN). In each subgroup 6 rats were treated with ACTH (18 micrograms/100 g B.W./d) from operation until autopsy. RCH has been evaluated by the arithmetical difference between the data determined in the right control kidney excised at UN and those determined in the left solitary kidney. In all the rats, hyperadrenocorticism increased significantly the weight of the solitary kidney and its content in protein and RNA. There was a significant decrease of the DNA content of the solitary kidney in the rats sacrificed 7 d. post-UN, treated with ACTH and drinking the saline solution. DNA was not affected by ACTH in the 7 other groups suggesting that ACTH favours cellular hypertrophy mainly in the rats drinking the saline solution. The renotrophic action of hyperadrenocorticism may be related to an altered handling of Na+ and K+: there was a positive correlation between the weight gain of the solitary kidney and the urinary excretion of Na+ (r = 0.507, p less than 0.001) and of K+ (r = 0.460, p less than 0.001). Hyperinsulinism was present in all the rats given ACTH; it may act as a growth factor. Hyperglycemia played an important role in former experiments but it was absent in the present studies.

Growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics with or without severe microvascular lesions.

Plasma levels of growth hormone (GH) were determined in fifty-two non obese insulin-dependent diabetics (IDD) and in twenty eight control patients before and after the i.v. administration of 250 micrograms in thyrotropin-releasing hormone (TRH). The mean basal plasma GH level in the IDD was normal. Administration of TRH elicited a rise of GH above 6 ng/ml in 40% of the IDD whereas no elevation occurred in any control subject. The basal and post-stimulative GH levels were similar in diabetics with mild retinopathy and in diabetics without microvascular lesions. The basal and peak plasma GH levels as well as the GH increase after TRH were significantly higher in ten patients with nephropathy and severe retinopathy than in 42 IDD having no detectable renal damage. It is concluded that there is a disturbance of GH secretion in IDD. This abnormality seems to be independent of the short-term glycemic control and appears to be partially related to the presence of severe microvascular lesions. The present results do not prove a causal relationship between the abnormal GH secretion and the development of the diabetic microangiopathy as the pituitary dysfunction could also be a consequence of central microvascular lesions.

[Hormonal adaptation to chronic self-starvation in patients with anorexia nervosa (author's transl)]. / Adaptations endocriniennes à la dénutrition chronique chez l'anorectique mentale.

An intravenous glucose tolerance test (glucose 0.33 g/kg bodyweight) was performed in 35 women with chronic anorexia nervosa (AN) and in 19 age-matched women of normal weight. Plasma free fatty acids (FFA), immunoreactive insulin (IRI) and growth hormone (GH) levels were measured before and after the test. Although the mean value of glucose disappearance rate K was significantly reduced in the patient group as compared with the control group, K was in fact normal (greater than or equal to 1.10 +/- 10(-2)) in 20 anorectic women (AN 1) and lowered in 15 (AN 2). The basal and post-stimulation IRI levels were decreased in all anorectic women, but particularly in the AN 2 group with impaired glucose tolerance. The glucose load elicited a striking rise in GH in patients of the AN 2 group, a slight increase in those of the AN 1 group and no change in women of the control group. FFA values before the test were high mainly in the AN 2 patients but the difference with reference values did not reach statistical significance owing to the large s.e.m. After the glucose load there was a similar decrease in FFA levels in all three groups, but levels in the AN 2 group remained significantly higher than in the control group. Hyposecretion of IRI and hypersecretion of GH may account for the impaired glucose tolerance observed in all patients of the AN 2 group. Both hormonal changes facilitate neoglucogenesis and lipolysis, thereby providing the energy substrates required for survival of the self-starved subjects. The anorectic women also had low plasma T3 enabling adjustment of the oxidative metabolism to the reduced food supply.

Impairment of renal compensatory hypertrophy by hypothyroidism in the rat.

Renal compensatory hypertrophy (RCH) occurs in hypothyroid rate, but it is impaired when compared to RCH found in euthyroid controls. It is due to cellular hypertrophy as the DNA content does not change and the Protein/DNA ratio increases in the compensating kidney. RCH is enhanced by thyroxine (T4) with a rise in the DNA content of the compensating kidney, but the Protein/DNA ratio does not change indicating that hypertrophy is as important as hyperplasia. Corticotrophin (ACTH) given to eu and hypothyroid rats enhances RCH with an increase in the protein content of the compensating kidney without any change in its DNA content. In the hyperthyroid rats, the enhanced RCH is not further increased by ACTH and the rise in the kidney DNA content elicited by T4 is suppressed by ACTH. The Protein/DNA ratio is increased by ACTH in hypo, eu and hyperthyroid rats. The renotrophic action of ACTH is due to hyperadrenocorticism: it is related to an increased plasma testosterone level and to a disturbed Na+, K+ and glucose metabolism.

[Influence of nutritional factors on the enhancement of renal compensatory hypertrophy by hyperadrenocorticism in the rat (author's transl)]. / Modulation de l'effet rénotrophique de l'hypercorticisme surrénalien par des facteurs nutritionnels chez le rat uninéphrectomisé.

In the rat compensatory hypertrophy (RCH) was enhanced by hyperadrenocorticism induced by the administration of a long acting ACTH at a dose of 18 Y/100 g body weight/d. for 7 d. after uninephrectomy (UN). In the present experiments we compared the differences delta between the weight, the content in protein, RNA and DNA of the left solitary kidney and the same determinations done on the right kidney excised at UN 7 d. earlier. The rats drank freely a isotonic solution of NaCl (G1) or KCl (G2) or glucose (G3, G4). The rats of group G1, G2 and G3 received a standard solid food; the G4 rats ate a K poor diet. About half of the animals were treated with ACTH. RCH occurred in all the rats even when they lost body weight. The pain in weight of the solitary kidney was enhanced in all the rats treated with ACTH but not in the G2 rats loaded with KCl. This renotrophic action of hyperadrenocorticism was most prominent in the K depleted G4 rats. The protein/DNA ratio, a marker of cellular hypertrophy, was increased by hyperadrenocorticism in the G1 and G2 rats drinking respectively the NaCl or the KCl solutions. This ratio did not change in the ACTH treated G3 and G4 rats drinking the glucose solution suggesting that, in this experimental condition, cellular hyperplasia and hypertrophy occurred at the same extent. These experiments suggest that, in the uninephrectomized rat, the renotrophic action of ACTH is modulated by nutritional factors. The enhancement of RCH by ACTH may be related to hyperglycemia, hyperinsulinism or altered handling of Na+ and K+ by the nephron.

[Correlation between renal compensatory hypertrophy and urinary sodium excretion in the ACTH treated rat]. / Corrélation entre l'hypertrophie rénale compensatrice et le débit urinaire de sodium chez le rat traité par l'ACTH.

In the rat, renal compensatory hypertrophy (RCH) is enhanced by the administration of ACTH (beta 1-24 corticotrophin) given at a dose of 18 micrograms/100 g. body weight/d. after uninephrectomy. In the rats drinking tap water, the enhancement of RCH by ACTH occurs without any significant change in urinary Na+ excretion. But, in the animals drinking a NaCl solution (9 g/l), ACTH determines a polyuria with hypernatriuria and a more striking increase of RCH positively correlated with the urinary Na+ excretion.

[Hyperthyroidism and subjects hyperresponding to thyrotropin. Importance of simultaneous thyrotropin and prolactin determination following administration of thyroid-releasing hormone]. / Hypothyroidie et sujets hyperrépondeurs en thyrotropine. Intérêt du dosage simultané de thyrotropine et de prolactine après thyrolibérine.

Primary hypothyroidism is assessed by increased basal and TRH-induced TSH levels. Since basal and TRH induced prolactin (PRL) levels may also be modified by the thyroid status, TSH and PRL responses to TRH are simultaneously determined in patients with mild or evident primary hypothyroidism (n = 22) and in TSH hyperresponders (n = 28) with clinicobiological appearance of euthyroidism. In evident hypothyroidism (free thyroxine index FT4 I = 0,4 +/- 0,1) basal PRL are increased in 8 out of 11 patients and TRH-induced PRL responses are exaggerated in all cases like in mild hypothyroidism (FT 4 I = 1,2 +/- 0, 1) A negative correlation is found between maximal PRL levels and triiodothyronine (T3) levels (p less than 0,01). In presumed euthyroid TSH hyperresponders (FT4 I = 2,2 +/- 0,1) PRL response to TRH is exaggerated in only 7 patients and no correlation exists between maximal PRL and T3 levels. These data suggest that simultaneously exaggerated TSH and PRL responses to TRH are presumably patterns of potential hyperthyroidism for the diagnosis of which the determination of TSH alone seems to be necessary but insufficient.

Influence of nutritional factors on the renotrophic action of ACTH in the uninephrectomized rat.

In the rat, renal compensatory hypertrophy (RCH) was apparent 48 h after uninephrectomy; it was significantly enhanced by long-acting beta1-24-corticotrophin (ACTH) when the animals had free access to food and a NaCl solution (9 g/l). In rats starved after uninephrectomy but drinking the NaCl solution freely, RCH was suppressed: the weights of the body, heart, liver, and solitary kidney were reduced. In similarly starved rats treated with ACTH, the weights of the heart and the solitary kidney were normal. RCH was also impaired in rats fed only a glucose solution (30 g/dl) after uninephrectomy, but it is restored by ACTH, which significantly increases the weight of the remaining kidney. This renotrophic action of ACTH may be related to hyperglycemia and, perhaps, elevated urinary K excretion, which occur in hyper-adrenocorticism and increase the work load of the nephron.

[Gastroparesis diabeticorum and bezoar (author's transl)]. / Gastroparésie diabétique et bézoards.

Gastroparesis diabeticorum has been isolated by Kassander in 1958. Since that time, 65 well documented cases have been published. Very often the patients are asymptomatic and the disorder is discovered by an occasional X-ray examination of the G-I tract. But, sometimes, the diabetes of these patients becomes brittle and they loose weight; bezoar, gastroplegia and hemorrhages may occur. We report two additional cases with severe undernutrition and bezoar. The gastroparesis may be related to a vagal neuropathie. The treatment is disappointing; metoclopramide gives the best improvement.