To test whether salivary tissue can secrete pituitary hormones, female Sprague-Dawley rats were hypophysectomized (hypox) and the following were transplanted to the sella turcica: parotid gland (group 3, n=33), adrenal gland (group 4, n=30), muscle (group 5, n=24). Group 2 (n=21) had the sella turcica filled with dentist's cement. In addition a group of rats (group 1, n=22) remained intact as controls. All groups were followed for 8 months. Daily vaginal smears showed normal cyclicity in controls and constant dioestrus in all hypox groups. Blood samples, taken once every 30 days before and after LHRH stimulation, showed significantly lower (P<0.001) plasma LH values in all hypox groups compared with controls. In group 3, a gradual and significant increase (P<0.05) was observed in the LH response to LHRH in parallel with a partial recovery of oestrous smears. No LH modification was observed in the other hypox groups. Plasma prolactin (PRL) levels were also very low in all hypox groups and were unaltered throughout the study. At the end of the experiments, half the animals were killed by decapitation and the hypothalamic-pituitary areas carefully dissected, homogenized and analysed for LH and PRL content. The remaining animals were perfused with 4% paraformaldehyde to obtain fixing of the whole body tissues. Hypothalamic and transplant areas were carefully dissected, frozen, cut and submitted to immunochemical procedures. LH content in the graft of group 3 animals was markedly (P<0.001) lower than in the control pituitary, but significantly higher (P<0.05) than in the other hypox groups. Immunochemistry showed LH and PRL positive cells in the graft of group 3 animals, whereas neither positive cells, nor LH content were observed in the parotid gland in situ. Experiments were completed with in vitro cultures of parotid glands in the presence or absence (controls) of synthetic hypothalamic hormones or rat hypothalamic extracts. After 1.5 weeks of culture, a significantly higher LH concentration (P<0.05) was observed in the wells treated with synthetic hypothalamic hormones (216+/-46 pg/ml vs 41+/-6 pg/ml in controls). When hypothalamic extracts were used, the LH levels increased more markedly (1834+/-190 pg/ml vs 36+/-6 pg/ml in controls) and those values were maintained during 3 weeks of culture. Immunostaining of these cultures showed a positive LH reaction in the epithelial cells found in the hypothalamic extract-treated wells. Both in vivo and in vitro studies confirm the transdifferentiation of parotid gland tissue to pituitary hormone-producing cells under hypothalamic influence.
JA Tresguerres, C Ariznavarreta, B Granados, P Alvarez-Vega, P Fernandez-Mateos, P Gil-Loyzaga, and R Alvarez-Buylla
C. A. ALVAREZ UGARTE, G. SORIANO, J. M. GIGLIO, and C. E. BOZZINI
Laboratorio de Hematología Experimental, Cátedra de Fisiología, Facultad de Odontología, Universidad Nacional de Buenos Aires, M. T. de Alvear 2142, Buenos Aires, Argentina
(Received 16 January 1976)
The importance of the kidney in the production of erythropoietin (erythropoiesis-stimulating hormone, ESH) in rodents has been demonstrated by a number of investigators (Krantz & Jacobson, 1970) since the initial observations of Jacobson, Goldwasser, Fried & Plzak (1957). The results of several studies indicate, however, that ESH can be produced in extrarenal sites after bilateral nephrectomy (Fried, Kilbridge, McDonald & Lange, 1969; Schooley & Mahlmann, 1972a), Erythropoietin activity is found in plasma of anephric rodents (Fried et al. 1969; Schooley & Mahlmann, 1972a) and man (Mirand, Murphy, Steeves, Weber & Retief, 1968; Naets & Wittek, 1968) when they are intensely stimulated, and this is due to production of ESH in extrarenal sites rather than release of preformed ESH from storage sites (Schooley &
A. ROSENKRANZ, C. E. BOZZINI, C. A. ALVAREZ UGARTE, M. A. MARTÍNEZ, and E. MAZZAFERRI
Cátedra de Fisiología, Facultad de Odontología, Universidad de Buenos Aires, and Departamento de Farmacología, Instituto Nacional de Farmacología y Bromatología, Buenos Aires, Argentina
(Received 10 June 1974)
Removal of the anterior pituitary in the rat has been shown to induce a decrease in the rate of red cell production (Bozzini, 1965) which in turn produces a reduction in the total circulating red cell volume (TCRCV) (Berlin, Van Dyke, Siri & Williams, 1950). Muldowney (1957), in man, and Doornenbal, Asdell & Comar (1962), in rats, have found that the TCRCV is better correlated to lean body mass (LBM) than to total body weight. Since not only hypophysectomy (Li, Simpson & Evans, 1949; Bozzini, Kofoed, Niotti, Alippi & Barrionuevo, 1970) but also testosterone treatment (Kochakian & Webster, 1958; Nathan & Gardner, 1965) result in profound alterations in body composition, which make it difficult to interpret TCRCV variations when its value is expressed
C Gonzalez, A Alonso, N Alvarez, F Diaz, M Martinez, S Fernandez, and AM Patterson
The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of both progesterone and 17beta-estradiol. However, it remains unclear whether estrogens alone or progestins alone can cause insulin resistance, or whether it is a combination of both which produces this effect. We attempted to determine the role played by progesterone and/or 17beta-estradiol on the phenomena of sensitivity to insulin action that take place during pregnancy in the rat. Ovariectomized rats were treated with different doses of progesterone and/or 17beta-estradiol in order to simulate the plasma levels in normal pregnant rats. A euglycemic/hyperinsulinemic clamp was used to measure insulin sensitivity. At days 6 and 11, vehicle (V)- and progesterone (P)-treated groups were more insulin resistant than 17beta-estradiol (E)- and 17beta-estradiol+progesterone (EP)-treated groups. Nevertheless, at day 16, the V, EP and E groups were more resistant to insulin action than the P group. On the other hand, the V, EP and E groups were more insulin resistant at day 16 than at day 6, whereas the P group was more insulin resistant at day 6 than at day 16. Our results seem to suggest that the absence of female steroid hormones gives rise to a decreased insulin sensitivity. The rise in insulin sensitivity during early pregnancy, when the plasma concentrations of 17beta-estradiol and progesterone are low, could be due to 17beta-estradiol. However, during late pregnancy when the plasma concentrations of 17beta-estradiol and progesterone are high, the role of 17beta-estradiol could be to antagonize the effect of progesterone, diminishing insulin sensitivity.
N. Torres, M. Fanelli, A. L. Alvarez, D. Santajuliana, S. Finkielman, and C. J. Pirola
Betamethasone was administered on alternate days to rats, and the role of the central cholinergic system in the development of hypertension assessed. After 15 days of treatment the systolic blood pressure of treated rats was significantly higher than that of control rats. Peripheral administration of atropine but not of methyl atropine reduced systolic pressure in glucocorticoid-treated rats and had no effect in controls. Therefore, [3H]quinuclidinyl benzylate binding, sodium-dependent high-affinity choline uptake and choline acetyltransferase studies were performed in the septal area, anteroventrolateral medulla (AVLM), anterior hypothalamic preoptic area (AH/PO) and hypothalamus. The density of muscarinic receptors was increased in the hypothalamus and AVLM of treated rats without significant changes in affinity. Choline acetyltransferase activity significantly decreased in the AVLM and increased in the AH/PO. In addition, a decrease in the hypothalamus and an increase in the AH/PO of sodium-dependent high-affinity choline uptake was observed in glucocorticoid-treated rats. These results suggest the presence of an enhanced muscarinic cholinergic activity in several brain nuclei in rats with glucocorticoid-induced hypertension. This activation could be due to pre- and post-synaptic hypersensitivity.
Journal of Endocrinology (1991) 129, 269–274
S Ramos, L Goya, C Alvarez, MA Martin, and AM Pascual-Leone
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 microg/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 microg/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 microg/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.
F Aréchiga-Ceballos, E Alvarez-Salas, G Matamoros-Trejo, M I Amaya, C García-Luna, and P de Gortari
Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus–pituitary–thyroid axis (HPT) is reduced, whereas that of the hypothalamus–pituitary–adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2–3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed by in situ hybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.