Biomedical subjects

C Ariznavarreta

Publications and source records attributed to C Ariznavarreta.

17 recordsLinked to original sources

PubMed2000

Recombinant human growth hormone enhances tibial growth in peripubertal female rats but not in males.

OBJECTIVE: A novel non-invasive technique termed microknemometry, which allows daily leg length measurement, was used to investigate the growth promoting effect of growth hormone (GH) on peripubertal rats. We compared the effect of different patterns of recombinant human (rh) GH administration to peripubertal male rats with the effect produced by two daily administrations of the same amount of rhGH to peripubertal female rats or adult male rats. Another group of peripubertal male rats was also submitted to a 3-day period of starvation, in order to study catch-up growth during refeeding and to determine whether this process could be stimulated by exogenous GH administration. RESULTS: GH treatment was unable to stimulate tibial growth or weight gain in peripubertal males, whereas a clear growth promoting effect was observed in female rats and also in adult male rats. Starvation caused a dramatic body weight loss, and a reduction in tibial growth rate. Peripubertal male rats gained body weight faster than unstarved animals during refeeding, although recovery was not complete after nine days. Tibial growth, however, was resumed at the same speed as in normally fed males. This means that no catch-up effect was observed after refeeding in animals either with or without GH treatment. CONCLUSIONS: During peripuberty, normal male rats grow at a maximal speed that cannot be further increased by exogenous GH treatment, whereas age-matched female rats or older males grow at a slower rate than peripubertal males. Thus, exogenous rhGH administration is capable of enhancing growth velocity.

Aging↗

PubMed1999

Parotid gland tissue is able partially to assume pituitary functions under the influence of hypothalamic factors: in vivo and in vitro studies.

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.

Adrenal Glands↗

PubMed1999

Salivary gland is capable of GH synthesis under GHRH stimulation.

Twelve female rats weighing approximately 150 g received in the submaxillary gland a pellet capable of releasing 3.5 microg GHRH/h for 60 days. Another eight sex- and weight-matched animals received placebo pellets in the same place. After two months the animals were killed, heart blood was collected and pituitary and submaxillary glands were carefully dissected. Pituitary GH content in both placebo- and GHRH-treated animals showed similar values, but plasma GH and IGF-I levels were significantly lower in the animals carrying GHRH pellets (P<0.03); these animals also had a significantly higher GH content in the submaxillary gland (19.2+/-8 ng/mg protein) compared with the placebo-treated group (1.1+/-0.3 ng/mg protein). GH mRNA was present only in the submaxillary gland of GHRH-treated rats as determined by PCR-Southern blot and by in situ hybridization methods. It is concluded that high local GHRH levels are capable of inducing transdifferentiation in submaxillary gland cells to synthesize GH.

Animals↗

PubMed1999

Effect of long-term GHRH and somatostatin administration on GH release and body weight in prepubertal female rats.

In order to find a chronic GHRH administration capable of stimulating growth rate without depleting pituitary GH content, prepubertal female rats were subcutaneously (sc) treated with GHRH (1-29)-NH2 and somatostatin (SS). In experiment 1, the rats received sc injections of GHRH and cyclic natural SS for 19 days. In the second study, female rats were continuously treated during 21 days with GHRH, using a slow release pellet, alone or combined with one daily injection of long acting SS (octreotide). In experiment 1, body weight was significantly increased when GHRH was administered at the highest daily dosage (1200 microg/day), accompanied by an slight increment in pituitary GH content. Hypothalamic SS concentrations decreased when GHRH or SS were administered alone whereas the combined treatment with both peptides did not modify this parameter, which suggests the existence of a balance between the chronic actions of both peptides on hypothalamus. In experiment 2, the continuous infusion of GHRH increased plasma GH levels and tended to enhance pituitary GH content. Nevertheless, GHRH effect was not effective enough to increase body weight. By adding one daily injection of SS both GHRH effects on the pituitary gland were abolished. Our study indicates that female rats retain responsiveness to chronic GHRH and SS treatments at both pituitary and hypothalamic levels.

Animals↗

PubMed1998

Sexual dimorphism in growth as measured by microknemometry: different responses to GH deficiency and exogenous GH administration.

To monitor growth, a novel noninvasive leg length measurement technique, called microknemometry, which allows daily observation of tibial growth rate, was used. The rat exhibits a striking sex-related difference in postpubertal growth. Exogenous GH administration results in a sexually dimorphic response, affecting growth in normal young female rats but not in males. Here we investigated how chronic GH deficiency affects male and female rat growth patterns. The degree of growth rate recovery was investigated after exogenous GH administration to chronically deficient males and females. The deficiency was induced by neonatal monosodium glutamate (MSG) treatment. Since the neonatal gonadal environment plays an important role in the dimorphic growth pattern, neonatal androgenization of female rats with testosterone or neonatal feminization of male rats by castration was performed and the growth pattern monitored. MSG treatment decreased pituitary GH content and plasma IGF I levels in both sexes, but caused a less marked reduction of female rat tibial growth and body weight gain than in males. Additionally, only MSG-treated males showed decreased pituitary LH content, so that the dimorphic action of MSG on the gonadal axis may contribute to the observed differences in growth rate. GH administration was able to increase leg length in all MSG-treated rats but was more effective in females, despite a similar restoration of plasma IGF I levels in both sexes. Although neonatal castration of male rats resulted in a reduction of tibial growth rate and body weight, and neonatal testosterone administration to female rats caused a slight increase in body weight, a complete modification of the gender-dependent growth pattern was not achieved, indicating that appropriate steroid environment is also needed in puberty and adulthood.

Animals↗

PubMed1995

Long-term behavioral effects of perinatal exposure to delta 9-tetrahydrocannabinol in rats: possible role of pituitary-adrenal axis.

This work evaluated motor behaviors in adult male and female rats exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. The possibility that perinatal THC exposure induces sensitization to other drugs of abuse has also been addressed by evaluating morphine place preference conditioning (MPP) in the adult offspring. Maternal exposure to THC resulted in long-term effects on motor behaviors such as rearing, grooming and sniffing, in the adult offsprings of both sexes. Additionally, female offspring exposed to THC showed greater locomotor activity than controls, when measured using an actimeter. THC-exposed males exhibited an increased exploratory behavior in a plus-maze paradigm. When the adult animals were tested for MPP, THC-exposed offspring of both sexes exhibited an enhanced sensitivity to the rewarding effects of a moderate dose of morphine (350 micrograms/kg), an effect which was more marked in the males. These results showed that perinatal exposure to this psychoactive cannabinoid affected motor behaviors in the adult, suggesting a psychomotor activation very similar to that observed after gestational exposure to other drugs of abuse. A possible role of a THC-induced hypothalamus-pituitary-adrenal (HPA) axis activation was also evaluated in the present study. THC-exposed females exhibited higher levels of both corticotropin releasing factor (CRF-41) in the medial basal hypothalamus (MBH) and plasma corticosterone, whereas THC-exposed males showed the lower levels of both endocrine parameters. Since glucocorticoids are important modulators of both brain development, and adult brain function, these results indicate a possible role of HPA axis disturbances in the mediation of the behavioral effects described after perinatal THC exposure.

Adrenal Glands↗

PubMed1994

Changes in serum growth hormone and prolactin levels, and in hypothalamic growth hormone-releasing hormone, thyrotropin-releasing hormone and somatostatin content, after superior cervical sympathectomy in rats.

After bilateral superior cervical ganglionectomy (SCGx) of adult male rats, norepinephrine (NE) content of the medial basal hypothalamus (MBH) decreased significantly by 39-47% from 16 h to 7 days after surgery. During this time the levels of serum growth hormone (GH) and prolactin (PRL) and of MBH GH-releasing hormone (GRH), thyrotropin-releasing hormone (TRH) and somatostatin were measured by RIA. In sham-operated controls, serum PRL increased and serum GH decreased 16-24 h after surgery, attaining pre-surgical levels later on. In SCGx rats, significantly lower serum GH and PRL and higher MBH GRH and TRH content as compared to controls was observed 16-24 h after surgery, during the wallerian degeneration phase after SCGx. MBH somatostatin concentration decreased in SCGx rats 20 h after surgery. Two injections of the alpha 1-adrenoceptor blocker prazosin 45 and 90 min before sacrifice, alone or together with the beta-blocker propranolol, prevented the changes in MBH hypophysiotropic hormone content, as well as in serum GH and PRL levels, found in SCGx rats 20 h after surgery. Propranolol treatment did not affect hormone levels. Neither drug modified the decrease in MBH NE content observed after SCGx. The results argue in favor of the existence of physiologically relevant projections from superior cervical ganglion neurons to the MBH controlling hypophysiotropic hormone release.

Animals↗

PubMed1991

Stress induced changes in testis function.

The mechanism through which chronic stress inhibits the hypothalamic-pituitary-testicular axis has been investigated. Chronic restraint stress decreases testosterone secretion, an effect that is associated with a decrease in plasma gonadotropin levels. In chronically stressed rats there was a decrease in hypothalamic luteinizing hormone-releasing hormone (LHRH) content and the response on plasma gonadotropins to LHRH administration was enhanced. Thus the inhibitory effect of chronic stress on plasma LH and FSH levels seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a modification in LHRH secretion. It has been suggested that beta-endorphin might interfere with hypothalamic LHRH secretion during stress. Chronic immobilization did not modify hypothalamic beta-endorphin, while an increase in pituitary beta-endorphin secretion was observed. Since we cannot exclude that changes in beta-endorphin secreted by the pituitary or other opioids may play some role in the stress-induced decrease in LHRH secretion, the effect of naltrexone administration on plasma gonadotropin was studied in chronically stressed rats. Naltrexone treatment did not modify the decrease in plasma concentrations of LH or FSH. These findings suggest that the inhibitory effect of restraint on the testicular axis is exerted at hypothalamic level by some mechanism other than opioids.

Adrenal Glands↗

PubMed1991

Naltrexone does not reverse the inhibitory effect of chronic restraint on gonadotropin secretion in the intact male rat.

There is considerable evidence suggesting that endogenous opioids may play an important role in acute stress-induced decreases in luteinizing hormone (LH) release. Studies were undertaken to analyze the role of endogenous opioids in chronic stress-induced decrease in circulating LH and follicle-stimulating hormone (FSH). Chronic restraint (6 h daily over 4 days) evoked a decrease in circulating LH and FSH. Naltrexone treatment, (2 mg/kg three times daily) during the 4 days of restraint, caused an increase in plasma concentrations of LH and FSH, and antagonized the LH suppressory effect of morphine (10 mg/kg) administration. Despite this, naltrexone treatment was ineffective in preventing the inhibitory effect of chronic restraint stress on circulating LH and FSH. Chronic restraint also induced a decrease in hypothalamic LH-releasing hormone (LHRH) content in saline-treated rats. On the contrary, in naltrexone-treated rats, chronic restraint evoked an increase in hypothalamic LHRH content. Thus endogenous opioids and chronic stress seem to act by different mechanisms on the hypothalamic LHRH neuron. In unstressed orchidectomized rats, naltrexone administration did not modify circulating LH, but increased plasma concentrations of LH in acutely restrained rats. These data suggest that endogenous opioids may mediate gonadotropin secretion during acute stress, but not during chronic stress.

Animals↗

PubMed1991

Influence of chronic restraint stress on pro-opiomelanocortin mRNA and beta-endorphin in the rat hypothalamus.

It has been postulated that some endocrine responses to stressful stimuli are mediated through the activation of hypothalamic pro-opiomelanocortin (POMC)-derived peptides. The aim of the present study was to analyse the effect of chronic stress on expression of the POMC gene in the medial basal hypothalamus and pituitary, and on serum concentrations of LH, beta-endorphin and corticosterone. Adult male rats were killed after being subjected to restraint stress for 6 h/day over 2, 3 or 4 days. Chronic restraint induced an increase in serum concentrations of beta-endorphin and corticosterone and a decrease in serum LH levels. To determine whether chronic stress induced any change in POMC synthesis, a dot-blot method was used to measure POMC mRNA levels. No significant changes were detected either in the beta-endorphin content or in POMC mRNA levels in the medial basal hypothalamus after 2, 3 or 4 days of chronic restraint. This observation contrasts with the stimulation of POMC mRNA levels in both lobes of the pituitary. The data suggest that although chronic restraint induces an increase in POMC synthesis and secretion in the pituitary and a decrease in LH secretion, it has no effect on hypothalamic POMC neurones.

Animals↗

PubMed1990

Role of LHRH in the gonadotrophin response to restraint stress in intact male rats.

A hypothalamic site of action has been hypothesized for the inhibitory effect of chronic stress on gonadotrophin secretion. The aim of the present study was to examine the temporal changes in hypothalamic LHRH content and gonadotrophin secretion during restraint stress, and the pituitary responsiveness to LHRH stimulation in chronically stressed rats. Adult male rats were killed after being restrained for 0, 20, 45, 90, 180 and 360 min or for 6 h daily over 2, 3 and 4 days. After 20-45 min of stress there was an increase in plasma concentrations of LH (P less than 0.01) and a decrease in hypothalamic LHRH content (P less than 0.01), suggesting a negative correlation between plasma LH and hypothalamic LHRH concentrations. Plasma concentrations of FSH were also increased by restraint, but the FSH response was slower and less than the plasma LH response, being significant after 90 min of restraint. Plasma LH and FSH and hypothalamic LHRH concentrations were decreased in chronically stressed rats. In rats restrained for 6 h daily over 4 days, the response of plasma gonadotrophins to administration of 500 ng LHRH was enhanced 45 min after the injection. On the basis of these observations we concluded that in the intact rat, stress may acutely stimulate LHRH and gonadotrophin secretion, and the inhibitory effect of chronic stress on plasma LH and FSH seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a decrease in LHRH secretion.

Animals↗

PubMed1989

Role of the adrenal cortex in chronic stress-induced inhibition of prolactin secretion in male rats.

The response of prolactin to chronic stress in intact, adrenalectomized and adrenomedullectomized male rats was studied. Immobilization stress in intact animals induced a significant increase in plasma concentrations of prolactin after 20 and 45 min and a significant decrease when the rats were submitted to chronic restraint (6 h daily for 4 days). Five weeks after adrenomedullectomy, plasma prolactin and corticosterone responses to chronic stress were not modified. In contrast, the inhibitory effect of chronic stress on prolactin secretion was totally suppressed by adrenalectomy. When treated with dexamethasone during the 4 days of restraint, adrenalectomized stressed rats showed similar plasma concentrations of prolactin to the intact stressed rats. These data indicate that the adrenal cortex is able to play an inhibitory role on prolactin secretion during stress only through a prolonged release of glucocorticoids.

Adrenal Cortex↗

PubMed1989

Effect of adrenomedullectomy and propranolol treatment on the response of gonadotrophins to chronic stress in male rats.

In order to study the involvement of the adrenal medulla in stress-induced inhibition of gonadotrophin secretion, we measured plasma concentrations of LH, FSH and corticosterone in adult male rats subjected to chronic restraint after surgical ablation of the adrenal medulla. In intact animals, chronic restraint (6 h daily over 4 days) induced a significant (P less than 0.05) decrease in plasma concentrations of LH, whereas plasma concentrations of corticosterone showed the expected significant (P less than 0.01) increase. Adrenomedullectomy did not significantly modify basal plasma concentrations of LH or corticosterone. In these rats, there was no significant decrease of LH after stress, while the increase in corticosterone was as significant as in sham-operated animals (P less than 0.01). In order to confirm the role of adrenomedullary catecholamines in stress-induced gonadotrophin inhibition another group of rats was treated s.c. with the beta-adrenergic blocker propranolol (2 mg/kg twice daily). These rats showed an attenuated inhibition of LH during stress similar to that observed in adrenomedullectomized rats. Levels of FSH were significantly reduced after stress in the saline-treated group, while there were no differences between stressed or unstressed rats in the propranolol-treated group. These results may be considered as evidence that medullary catecholamines, acting through beta-receptors, are factors involved in gonadotrophin inhibition during chronic stress.

Adrenal Medulla↗

PubMed1989

[Response of plasma and retinal somatostatin to insulin-induced hypoglycemia in diabetic and control rats].

Changes in plasmatic levels and retinal content of somatostatin after insulin-induced hypoglycemia were investigated in three different groups of animals: Control group (C), Diabetic untreated group (D); and, Insulin-treated diabetic group (DI). In addition, another group of animals, not submitted to hypoglycemia, was used as control reference of retinal prehypoglycemic content of somatostatin (group B). Plasmatic basal levels of somatostatin were slightly higher in group DI, and significantly higher in group C, whereas they did not show any differences in group D and DI after hypoglycemia, being significantly higher in group C. The somatostatin retinal content is similar in animals not subjected to hypoglycemia and in the C and DI groups after hypoglycemia, where the rats of the D groups showed significantly higher values than the remainder of the experimental groups, an effect that is also evident in nontreated diabetic animals, even if they are not subjected to hypoglycemia, Summing up, the plasmatic somatostatin response to insulin-induced hypoglycemia is impaired in diabetic rats. Retinal somatostatin content is unchanged after hypoglycemia.

Animals↗

PubMed1987

Gonadotropin inhibition during chronic stress: role of the adrenal gland.

The effect of adrenalectomy, metyrapone and dexamethasone treatments on gonadotropin response to chronic stress were studied. Adult male rats were submitted to chronic restraint (6 h daily over 4 days). At the end of the last stress period animals were decapitated and trunk blood was collected. Chronic restraint evoked a decrease in plasma LH and to a lesser degree in plasma FSH in the intact rat. Adrenalectomy did not prevent the LH reduction induced by stress and magnified the inhibitory effect of restraint on FSH secretion. Administration of the corticosterone synthesis blocker metyrapone increased the inhibitory effect of restraint on plasma LH and to a lesser degree on plasma FSH. Dexamethasone treatment did not significantly modify plasma gonadotropin levels in adrenalectomized unstressed rats, but this treatment totally blocked plasma LH and FSH reduction after chronic restraint. These results indicate that plasma LH and FSH reduction during chronic restraint is not due to the increase in glucocorticoid secretion, but seems to be mediated by the increase of the hypothalamic-pituitary components of the adrenal axis.

Adrenal Glands↗

PubMed1987

Influence of streptozotocin-induced diabetes on the concentration of immunoreactive somatostatin in the retina and peripheral blood of the rat: effect of insulin treatment.

Changes in somatostatin-like immunoreactivity (SLI) were examined in the retina and peripheral blood of diabetic rats treated with streptozotocin (STZ) and insulin. There was no change in retinal SLI content at 4 and 11 days after administration of STZ but, thereafter, SLI increased progressively in the diabetic animals by 220% at 18 days and 300% at 27 days. Plasma SLI levels increased by 500% at 11 days and maintained similar levels thereafter. Diabetic animals treated with insulin (3-5 i.u. daily) for 27 days showed a significant (P less than 0.01) decrease of retinal and plasma SLI levels compared with untreated diabetic animals. It is concluded that there is a significant increase of retinal and plasma SLI levels in diabetic rats which tends to normalize after several days of insulin treatment.

Animals↗

PubMed1987

Gastric mucosal somatostatin-like immunoreactivity in peptic ulcer.

Somatostatin (SS) has been reported to exert potent inhibitory effects on gastric acid, pepsin and gastrin secretion. Although still controversial, the results of several studies have shown a possible influence of a local decrease in gastric somatostatin in the physiopathologic characteristics of peptic ulcer disease. In the present study, immunoreactive SS content (SLI) of antral (SLI-a), corpal (SLI-c) and fundic (SLI-f) mucosal extracts was measured by radioimmunoassay (RIA) in control patients (C) and in those patients with duodenal ulcer (DU) or gastric ulcer (GU) to further study a possible role of SS in peptic ulcer disease. Fifty-five patients (C = 20, DU = 21 and GU = 14) were included in the study. Gastric mucosal samples were obtained either by endoscopic biopsy (4.6 +/- 0.2 milligrams of weight) or operation (52.3 +/- 3.8 milligrams of weight). RIA was performed after a modified Arimura's method and results were expressed as nanograms per milligram of tissue plus or minus standard error of the mean. Chromatographic analysis of gastric mucosal extracts was performed on a Sephadex G-25 fine column. A great interindividual variation in SLI levels was observed (a range of 0.02 to 5.30 nanograms per milligram of weight). The mean SLI concentrations were: C (SLI-a, 2.55 +/- 0.45, SLI-c, 0.99 +/- 0.46 and SLI-f, 1.03 +/- 0.21); DU (SLI-a, 0.48 +/- 0.16, SLI-c, 0.43 +/- 0.13, and SLI-f, 0.58 +/- 0.12), and GU (SLI-a, 1.10 +/- 0.25, SLI-c, 0.40 +/- 0.10, and SLI-f, 0.81 +/- 0.24). Significantly greater amounts of SLI contents were found in the antrum of control patients as compared with those found in the corpus or fundus (p less than 0.05 and p less than 0.01, respectively). SLI-a levels were lower in peptic ulcer patients (DU, p less than 0.001 and GU, p less than 0.05) than in control patients. There was also a significant difference between SLI-a levels in DU versus GU patients (p less than 0.05). No significant differences were found in SLI-c and SLI-f contents in all three groups studied. In conclusion, these results suggest that decreased SS levels in antral gastric mucosa could be the alteration underlying the various physiopathologic mechanisms involved in the development of peptic ulcer disease.

Adult↗