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Biomedical subjects

A I Esquifino

Publications and source records attributed to A I Esquifino.

At least 19 recordsLinked to original sources

Changes in lymphoid organs of Ames dwarf mice after treatment with growth hormone, prolactin or ectopic pituitary transplants.

This study was performed to obtain more insight into the roles of PRL and GH in the control of immune functions in hereditary dwarf mice characterized by severe immunodeficiency. Adult female Ames dwarf mice (df/df) were injected daily for 10 days with ovine PRL (oPRL), bovine GH (bGH), oPRL+bGH or were implanted with a normal pituitary under the kidney capsule for 5 days. Only the treatment with bGH resulted in significant increases in the gain of body weight, and in absolute and relative thymus and spleen weights. Treatment with oPRL alone did not affect body weight gain or thymus and spleen weights. Treatment with oPRL+bGH produced a significant increase in the gain of body weight and in absolute and relative spleen weight but these effects were smaller than those measured in dwarf mice treated with bGH alone. Only bGH therapy resulted in extensive recovery of the absolute number of lymphocytes in the thymus and spleen of dwarf mice, with the values in treated dwarf mice not significantly different from those found in normal non-dwarf females. However, when these values were corrected for body weight, both the splenic and the thymic indices exceeded the values found in normal mice. The absolute numbers of lymphocytes in the spleen were also increased by oPRL+bGH treatment, but did not reach the values found in normal mice; however, the splenic index exceeded the values found in normal animals. Surprisingly, the absolute and relative numbers of lymphocytes found in the thymus of dwarf mice under oPRL+bGH therapy were indistinguishable from those found in oPRL or vehicle treated dwarf mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of treatment of normal and hyperprolactinemic rats with cyclosporine in vivo on the release of gonadotropins and prolactin from their pituitaries in vitro.

Cyclosporine (CyA) is extremely useful as an immunosuppressant and it is believed that at least some of its actions are due to antagonizing PRL effects. To determine whether the reported ability of CyA to inhibit gonadotropin release can be modified by PRL, we have examined the effects of treatment of normal and hyperprolactinemic rats with CyA in vivo on the release of LH, FSH and PRL from their pituitaries in vitro. Hyperprolactinemia was induced by implantation of capsules containing diethylstilbestrol (DES) and the animals were examined while the capsules were still in place (DES-IN) or after they had been removed (DES-OUT). Treatment with CyA significantly reduced plasma LH levels in control DES-IN rats without reducing basal LH release from the pituitaries of these animals in vitro. In the DES-IN rats, CyA exposure in vivo did not modify plasma PRL levels, but reduced PRL release in vitro, and interfered with the inhibitory action of dopamine (DA) on PRL release. The effect of DA on gonadotropin release in vitro was modified by CyA treatment. Administration of CyA failed to antagonize the suppressive effects of hyperprolactinemia on plasma LH and FSH levels or on the basal rates of gonadotropin release by incubated pituitaries. We conclude that CyA can reduce PRL release but does not interfere with the actions of PRL on anterior pituitary function.

Animals

Serum prolactin and luteinizing hormone levels and the activities of hypothalamic monoamine oxidase A and B and phenylethanolamine-N-methyl transferase are changed during sexual maturation in male rats treated neonatally with melatonin.

Male rat pups were given a single dose of melatonin on day 5 of age. On days 30, 45, and 60, prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were measured in serum and monoamine oxidase A (MAO A) activity, monoamine oxidase B (MAO B), and phenylethanolamine-N-methyl transferase (PNMT) activity were measured in the hypothalamus. Melatonin administration increased serum PRL levels at all ages studied. Serum LH levels were decreased in the melatonin treated group on day 30, but levels were elevated on days 45 and 60 of age as compared to controls. LH response to luteinizing hormone-releasing hormone (LHRH) only increased in melatonin treated animals at 30 days of age. Serum T levels decreased with melatonin treatment at 30 days of age, but increased on days 45 and 60 of age. T response to human chorionic gonadotropin (hCG) was blunted by melatonin treatment at 30 days of life. Hypothalamic MAO A activity increased, after neonatal melatonin administration, at 30 and 45 days of age and decreased at 60 days of life. Early neonatal melatonin administration increased MAO B and PNMT activities on day 45. These findings suggest that neonatal melatonin administration induces an earlier sexual maturation in male rats, possibly related to PRL, LH, MAO, and PNMT increases.

Animals

Evidence that circadian variations of circulating melatonin levels in fetal and suckling rats are dependent on maternal melatonin transfer.

Although the circadian variation of melatonin content in the pineal gland appears during the 3rd week of extrauterine life, recent studies suggest that the fetus perceives the day length through maternal melatonin transfer. Accordingly, we determined serum melatonin concentrations in pregnant and lactating rats and in their offsprings during the day (D) and at night (N). As compared with nonpregnant adult female rats (D: 6.0 +/- 0.5 and N: 112.0 +/- 5.0 pg/ml), significant increases of serum melatonin concentrations, both during the day and at night, were observed in 21-day pregnant (D: 21.0 +/- 2.6 and N: 222.0 +/- 7.2 pg/ml) and in 10-day (D: 20.0 +/- 2.6 and N: 145.0 +/- 12.3 pg/ml) and 20-day (D: 19.0 +/- 1.2 and N: 140.0 +/- 8.0 pg/ml) lactating animals, while a profound decrease was found in 5-day (D: 13.0 +/- 1.0 and N: 50.0 +/- 5.6 pg/ml) lactating rats. In addition, melatonin levels were significantly higher during the night than during the day in all the experimental groups. High levels and circadian variation of serum melatonin were detected also in 21-day-old fetuses (D: 13.0 +/- 0.8 and N: 108.0 +/- 4.8 pg/ml) and in 5- and 10-day-old suckling (in 5-day-old, D: 13.0 +/- 0.6 and N: 71.0 +/- 3.1 pg/ml; in 10-day-old, D: 17.0 +/- 1.4 and N: 63.0 +/- 3.8 pg/ml) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of hyperprolactinemia on prolactin and LH pulsatile pattern in female rats.

Prolactin (PRL) and luteinizing hormone (LH) secretions are very closely-related. To further understand these mechanisms, the pulsatile secretion pattern of both hormones in experimentally-induced hyperprolactinemia has been studied in adult female rats. Hyperprolactinemia was induced by the transplanting of two pituitary glands. Nine days after the transplant operation, rats were bled (75 or 100 microliters/7 min for 3 h). Serum samples were analyzed for prolactin and LH values by RIA. Hyperprolactinemia modifies pulsatile PRL secretion by increasing the absolute amplitude and duration of the peaks together with a decrease in their frequency. Also, the mean values of the hormone during the whole studied period were increased. Hyperprolactinemia was followed by an increase in the mean values of LH and in the absolute amplitude of the peaks. All these results suggest that hyperprolactinemia induced by pituitary grafting in adult female rats, is followed by a significant change in prolactin and LH pulsatility, which may explain, to some extent, the effects of hyperprolactinemia on reproduction.

Animals

Effect of cyclosporine on ornithine decarboxylase activity in rat submaxillary lymph nodes: modulation by sympathetic nerves.

In order to examine whether cyclosporine activity in submaxillary lymph nodes is dependent on sympathetic modulation, rats received a unilateral superior cervical ganglionectomy together with a contralateral sham-operation. Two weeks later, cyclosporine (5 or 20 mg/kg per day s.c.) was injected for five days. Freund's complete adjuvant was injected 1 h before the third injection of cyclosporine and the rats were killed 2 h after the last injection of cyclosporine. A significant increase in ornithine decarboxylase activity in submaxillary lymph nodes was observed two weeks after sympathetic denervation. Cyclosporine decreased enzyme activity in submaxillary lymph nodes on the sham-operated side by 67-77% and by 21-41% on the denervated side (P less than 0.01). The incorporation of [35S]methionine into proteins in ipsilateral submaxillary lymph nodes was increased by unilateral superior cervical ganglionectomy and decreased by cyclosporine to a similar extent in denervated and innervated lymph nodes. Superior cervical ganglionectomy decreased by about 93-95% the norepinephrine content of submaxillary lymph nodes regardless of cyclosporine treatment. The results indicate that an appropriate sympathetic neural environment is needed for cyclosporine to have an effect on ornithine decarboxylase activity in lymphoid tissue.

Animals

Slower growth of tumours in sympathetically denervated murine skin.

In order to examine tumour growth in sympathetically denervated murine skin, two breast cancer tumour lines were employed, i.e. M3 tumours, of a relatively high local growth and low metastatic capacity, and MM3-LN tumours, that grew locally at a slower rate but disseminated early to the lung. Mice subjected to unilateral superior cervical ganglionectomy or sham-operation 2 weeks earlier were used. M3 or MM3-LN tumours were implanted in the ipsilateral ear to the surgical procedure. Tumour size was assessed every 2-6 days, starting from the 7th day after tumour implantation. Growth of M3 and MM3-LN tumours was significantly slowed by a previous sympathetic denervation of the skin territory. There were no significant differences in the number or size of pulmonary metastases at autopsy between mice subjected to ganglionectomy or to sham-operation. Ganglionectomy increased significantly ipsilateral submaxillary lymph node ornithine decarboxylase activity by 62% and decreased noradrenaline content to 8% of the innervated contralateral lymph node. The present results indicate a local inhibitory modulation of tumour growth by the sympathetic nervous system.

Adenocarcinoma

Elevated corticosterone levels in transgenic mice expressing human or bovine growth hormone genes.

Ectopic expression of human or bovine growth hormone (GH) genes in 6 lines of transgenic mice was associated with a significant increase in plasma corticosterone levels. Elevated corticosterone levels were detected in both sexes under basal conditions and after ether stress. The adrenal activity of 3 beta-hydroxysteroid dehydrogenase was measured in two of these lines and was found to be significantly increased in transgenic animals. Plasma corticosterone levels in transgenic mice did not correlate with known differences between the various lines in male and female fertility or in the life span.

3-Hydroxysteroid Dehydrogenases

Anterograde nerve degeneration after superior cervical ganglionectomy coexists with a decrease in arginine vasopressin release in rats.

After bilateral superior cervical ganglionectomy (SCGx) in adult male rats, norepinephrine content of the pituitary neurointermediate lobe (NIL) decreased at 12-24 h after surgery to attain concentrations 40-60% of controls between 24 and 60 h after surgery. To assess arginine vasopressin (AVP) secretion during this time, plasma and NIL-AVP levels were measured by radioimmunoassay. In sham SCGx controls, plasma AVP increased about 2-fold within 6 h after surgery and decreased thereafter, to attain presurgical values by 60 h after surgery. In SCGx rats, a significant increase in plasma AVP concentration was observed at the 6th h after surgery, as compared to presurgical concentrations, with a decrease to values significantly lower than those of presurgical controls at 16-18 h after SCGx. As compared to sham-operated rats, significantly higher plasma AVP levels 6 h after surgery and significantly lower plasma AVP levels 16-24 h after surgery were found. NIL-AVP concentration in SCGx and sham-operated ras were significantly lower than presurgical levels at 6 h after surgery. SCGx rats had significantly higher amounts of AVP in NIL at 16-24 h after surgery. The changes in plasma and NIL-AVP levels found 6 or 16 h after SCGx or sham SCGx were unaffected by a prior pinealectomy. 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 increase in plasma AVP found in SCGx rats 6 h after surgery, and the decrease in plasma AVP and the increase of NIL-AVP found 16 h after SCGx.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ectopic pituitary transplants restore immunocompetence in Ames dwarf mice.

This work was undertaken to study the effects of prolactin on immune function in Ames dwarf mice. For that purpose, adult Ames dwarf mice were implanted with pituitaries from normal mice under the kidney capsule. Ectopic pituitary transplants produced the expected increase in plasma prolactin levels in male and female dwarf mice as compared to sham-operated dwarf or untreated normal mice. Body weight was significantly increased in pituitary-grafted dwarf mice of both sexes, but did not reach the values found in normal (non-dwarf) animals. Pituitary transplants induced an increase in thymus weight and in the number of lymphocytes in the thymus in dwarf mice of both sexes as compared to sham-operated dwarf controls. The weight of the thymus in grafted dwarf mice remained below values found in normal mice, while the number of thymic lymphocytes became indistinguishable from those recorded in normal mice. Effects of pituitary transplants on the spleen were similar to those described for the thymus; however, neither the weight nor the lymphocyte number in pituitary-grafted dwarfs reached the values found in normal animals. Natural killer activity of spleen lymphocytes from pituitary-grafted male and female dwarf mice was greatly enhanced as compared to lymphocytes from sham-operated dwarfs. This effect was greater in males than in females. The number of white blood cells in pituitary-grafted male dwarf mice was increased and indistinguishable from the values found in normal males. Surprisingly, this effect was absent in the females. These findings suggest that hormones secreted by the transplants, most likely prolactin and growth hormone, can enhance the immune response. This action may be mediated by direct action of prolactin and/or growth hormone on immune cells or by indirect effects.

Animals

Time-dependent effects of increased serum prolactin levels on corticosterone synthesis and secretion in male rats.

To investigate the role of prolactin (PRL) on adrenal cortex function, male rats of the Wistar strain were rendered hyperprolactinemic by the grafting of one pituitary gland under the kidney capsule at 30 days of life. Age-matched animals were sham-operated to be used as controls. The well known increase of serum PRL levels, in grafted rats, observed in samples taken at 10 a.m. was only maintained at 2 a.m. on days 2, 4 and 14 after grafting, when compared to sham-operated rats. A differential time-dependent effects was observed for corticosterone (B) secretion. An increase in adrenal B content is observed during the whole period studied in grafted animals, as compared to sham-operated animals being statistically significant on days 2, 4, 14 and 40 days after the transplant operation. A biphasic pattern is described for serum B levels: whereas increased serum B levels were found on days 2 and 8 of the experimental period; a decrease in serum B levels were found in the chronic situation. The expected increase in adrenal weight was not sustained over the whole period studied being only increased on days 4, 8 and 30 after the grafting. All these data suggest that PRL exert a time-dependent modification in B secretion from the adrenal gland.

Adrenal Glands

Melatonin effects on prolactin secretion in pituitary-grafted female rats.

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration of PRL secretion in pituitary-grafted female rats. Melatonin administration resulted in a marked and rapid decrease of previously high plasma PRL levels in pituitary-grafted rats. Luteinizing hormone releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in both sham-operated and grafted animals given saline whereas a statistically significant increase was observed in grafted, melatonin-treated rats. Estradiol benzoate administration caused an increase in plasma PRL levels of greater magnitude in the afternoon than in the morning in sham-operated animals given saline whereas in grafted animals no response to estradiol benzoate was detected. Melatonin increased the plasma PRL response to estradiol benzoate in sham-operated rats as compared to vehicle-treated animals. A normalization of PRL response to estradiol benzoate was shown in melatonin-treated, pituitary grafted rats. While the suppressive effects of melatonin in plasma PRL levels of pituitary-grafted animals is substantial the mechanism of this inhibition remains unknown.

Animals

Regulation of GH and TSH release from hyperplastic and ectopic pituitaries: effects of dopamine in vitro.

This study was undertaken to examine the consequences of prolonged removal of the pituitary from hypothalamic control and of estrogen-induced pituitary tumors on the susceptibility of GH and TSH release to regulatory influences of dopamine (DA). Adult male Fischer 344 rats were treated with transplants of female anterior pituitaries under the renal capsule or with Silastic capsules containing diethylstilbestrol (DES). Capsules with DES remained in place until the animals were killed (DES-IN) or were removed 7 weeks prior to sacrificing the rats (DES-OUT). Both pituitary grafts and DES caused the expected elevation in plasma prolactin and suppression of plasma GH and TSH levels. Basal GH release in vitro was not affected by exposure to DES in vivo but was reduced by transplantation of the pituitary to an ectopic site. Treatment with DA in vitro suppressed GH release from the in situ pituitaries of control, DES treated and grafted rats but increased GH release from the ectopic pituitaries. Basal release of TSH in vitro was reduced in the pituitaries of DES-IN and DES-OUT animals but was not affected by the presence of pituitary transplants. No detectable TSH was released from the ectopic pituitaries in the absence of DA. DA decreased TSH release from the pituitaries of control, DES-OUT and DES-IN rats but not from the in situ pituitaries of grafted rats. In contrast, DA produced an increase in TSH release from ectopic pituitaries. These results demonstrate that somatotrophs and thyrotrophs removed from the hypothalamic influences on subjected to direct and indirect effects of DES exhibit abnormal responses to DA. We suspect that prolonged absence of normal pituitary control leads to the development of regulatory mechanism of pituitary hormone release which are different from those operating under physiological conditions.

Animals

Possible prolactin-mediated effects of melatonin on gonadotropin secretion in the rat.

Melatonin administration to pituitary-grafted male and female rats resulted in a marked decrease of previously high plasma prolactin levels, while an increase in prolactin levels was observed in sham-operated controls. The latter effect was significant only in males. Treatment with melatonin did not modify basal LH hormone levels or LH responses to luteinizing hormone-releasing hormone (LHRH) in sham-operated rats of either sex. However, in pituitary-grafted females, melatonin increased both basal and LHRH-stimulated LH levels towards values recorded in sham-operated controls. No effects on basal LH levels were detected in grafted males under melatonin treatment, but the response of LH to LHRH was markedly increased and no longer differed from the values measured in sham-operated control animals pretreated with saline. Melatonin did not affect follicle stimulating hormone (FSH) levels except for an increase in FSH response to LHRH in grafted females. These findings suggest the existence of sex-dependent effects of melatonin on LH and FSH secretions. These effects of melatonin may be mediated by the different plasma prolactin levels in pituitary-grafted and sham-operated rats.

Animals

Changes in the catecholamine metabolism in the adrenal medulla of male hamsters with experimental hyperprolactinemia.

1. Prolactin (PRL) can play a role as a physiological modulator of adrenal medulla function in several rodents. 2. We have examined the effects of hyperprolactinemia induced by ectopic pituitary grafts in Syrian hamsters on the adrenal medulla contents of catecholamines (CA) and their metabolites, as well as on the activities of several enzymes involved in the metabolism of these amines. 3. Increases in the peripheral levels of PRL in these animals were associated with decreases in adrenal medulla weight and increases in adrenal medulla contents of norepinephrine, epinephrine and vanilmandelic acid, the main degradative metabolite of CA, while adrenal medulla contents of the O-methylated derivatives of CA, normetanephrine and metanephrine, were unaltered. 4. These changes were correlated with increases in the adrenal medulla activity of monoamine oxidase, while the activities of tyrosine hydroxylase, phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase were unaltered. 5. These results indicate that PRL is able to act on the adrenal medulla of hamsters by increasing the ability of these cells to metabolize CA via oxidative deamination.

Adrenal Medulla

Effects of diethylstilboestrol on testicular function and luteinizing hormone receptors.

Adult male Fisher-344 rats were implanted with DES-filled or empty Silastic capsules. After 14 weeks, capsules were removed and a second group of rats received DES capsules. Seven weeks later, all the rats were sacrificed. DES treatment decreased body, testes and seminal vesicle weights, and removal of the capsules partially restored the weight of these organs. The concentration of testicular LH receptors was increased by DES treatment. Circulating PRL levels were increased and gonadotropin levels were reduced in all animals having received DES at anytime. Plasma testosterone (T) levels were similar in all groups, but testicular T levels were reversibly decreased by DES. Similarly, whereas basal incubation media T levels were unchanged by DES treatment, the steroidogenic response in vitro to hCG was abolished by the presence of DES, and removal of the capsules restored this response. It appears that in this animal model DES and PRL exert opposing effects on testicular LH receptor.

Animals

Time-dependent effects of alcohol on the hypothalamic-hypophyseal-testicular function in the rat.

Adult male rats were followed throughout ethanol administration, in order to examine the time-dependent effects of ethanol on the hypothalamic-pituitary-gonadal axis. The results indicate that there is an increase in plasma prolactin levels together with a reduction in basal plasma luteinizing hormone (LH) levels, which are evident from the beginning of the intoxication period. An exaggerated response of LH to luteinizing hormone-releasing hormone was also evident from 2nd week on, in ethanol-treated rats. Basal and human chorionic gonadotropin-stimulated plasma testosterone levels were decreased in alcohol-treated as compared to control rats, at all time points studied. In addition, plasma estradiol levels were increased in ethanol-fed rats. These data suggest a direct suppressive effect of ethanol on LH release in the beginning of the intoxication period. Subsequent elevations of plasma estradiol and prolactin levels may have contributed to the maintenance of hypogonadism at the end of the intoxication period.

Animals

Melatonin effects on prolactin secretion in pituitary-grafted male rats.

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration on PRL secretion in pituitary-grafted male rats. Melatonin administration 5 hours before dark resulted in a marked decrease of previously high basal plasma PRL levels in pituitary-grafted rats, whereas a marked increase was detected in sham-operated animals. Vehicle treatment did not modify basal PRL values in grafted or sham-operated animals. Luteinizing hormone-releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in vehicle-treated, sham-operated or grafted rats, as well as in melatonin-treated sham-operated rats. An increase in PRL levels was shown in grafted rats treated with melatonin. Estradiol benzoate (EB) administration resulted in an increase in plasma PRL levels both in sham-operated and grafted vehicle-treated rats. No PRL response could be detected in sham-operated, melatonin-treated animals after EB administration. In pituitary-grafted animals given melatonin, PRL response to EB administration was slight and delayed. From these data, melatonin appears to modify PRL secretion through multiple complex mechanisms that may depend on the physiological status (hormonal and neurotransmitter) of the animals. A direct effect at the pituitary level altering lactotroph sensitivity seems to be one plausible explanation for the current findings, although an hypothalamic site of action cannot be excluded.

Animals