摘要:

The content of insulin-like growth factors, IGF-I and IGF-II, was measured in tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15. Serum IGF-I was elevated in tumor-implanted rats [2,557 ± (SE) 419 vs. 891 ± 100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 ± 16 ng/g) in comparison to control liver tissue (160 ± 5 ng/g) or control pituitary (80 ± 3 ng/g). The IGF-I levels were significantly increased in most peripheral tissues in the tumor-bearing rats with the exception of the liver. In support of this finding, messenger RNA for prepro IGF-I was likewise not increased in the livers of tumor-bearing rats, nor was there an increase in the growth hormone-dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All tumors had detectable levels of prepro IGF-I mRNA which was, however, less than 50% of that noted in normal control liver. The tumors also expressed an IGF-BP which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF-II were similar in control and tumor-bearing animals (–70 ng/ml). IGF-II levels in the tumor (90 ± 5 ng/g) were significantly higher than levels in control liver (34 ± 2 ng/g), but similar to those found in normal pituitary (165 ± 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively increased in skeletal muscle and heart of tumor-bearing rats. These data demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the liver does not appear to be stimulated over control levels by high serum growth hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are increased in livers of tumor-bearing rats. This suggests that the increase in serum IGF-I in these animals is due to increased production of IGF-I by the tumors themselves and by nonhepatic peripheral tissues and further that hepatic responsiveness to growth hormone is diminished in these tumor-bearin

ISSN:0028-3835    

DOI:10.1159/000126306

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In vitro and in vivo studies in rodents and human suggested an immunostimulatory effect of prolactin. The aim of the present study was to determine the impact of chronically elevated serum prolactin concentrations on the immune system in patients with prolactinomas. For this purpose parameters of the humoral and cellular immune system were studied in seven patients with prolactinomas on two occasions (1) when their serum prolactin concentration had been normalized through treatment with dopamine agonists and (2) when their serum prolactin concentration was high. Serum concentrations of immunoglobulines, interleukin 1, 3 and 6, TNF-α, interferon-γ and the soluble interleukin 2 receptor, leukocyte subsets and the natural killer cell activity were found to be within the normal range on both occasions, i.e. at normal and at high serum prolactin concentrations. The assumption could be made that long-lasting elevation of serum prolactin concentration induces adaptive changes when the acute stimulatory effects of prolactin on several parameters of the immune system have subside

ISSN:0028-3835    

DOI:10.1159/000126307

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

During aging female rats enter an anovulatory condition with chronically elevated circulating levels of estrogen described as persistent estrus (PE). Since this endocrine state is dramatically different from the fluctuating steroid milieu of young regularly cycling females, interpretations of altered neuroendocrine responses in aged rats have been difficult to attribute to aging per se. In the present study, young cyclic and middle-aged PE rats were treated with an LHRH agonist, [DTrp6, Pro9-NHEt]-LHRH, continuously (2.5 µg/h) for 12 days to suppress gonadotropin and ovarian steroid secretion. On the evening of the first day of LHRH agonist (LHRH-AG) treatment both young cyclic and middle-aged PE rats showed marked (p < 0.01) increases in plasma LH and FSH followed by progressive decreases in gonadotropin secretion which reached significantly (p < 0.05) lower levels than pretreatment values by day 7. LHRH-AG treatment significantly (p < 0.01) reduced circulating 17β-estradiol (E2) levels in both young and PE rats while progesterone concentrations did not change. Following LHRH-AG treatment, ovariectomy (OVX) resulted in increases of plasma LH and FSH that were delayed and attenuated in PE rats as compared to those of young females. When compared to non-treated rats, 12 days of LHRH-AG treatment in both young and PE females had a minimal and transient effect on the post-OVX gonadotropin responses, suggesting that the endocrine status immediately prior to OVX does not profoundly influence the post-OVX responses in young cyclic and middle-aged PE rats. Furthermore, LHRH-AG treatment does not appear to have permanent inhibitory effects on the hypothalamic-pituitary axis. Following LHRH-AG treatment in intact rats, the rebound in FSH secretion was delayed and prolonged in PE females and these rats did not return to estrous cyclicity. The results of these studies indicate that the neuroendocrine responses to the removal and return of ovarian negative feedback are impaired in PE rats, and suggest that these rats have a permanent dysfunction in the hypothalamic-pituitary-ovarian axi

ISSN:0028-3835    

DOI:10.1159/000126308

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We have previously found that proenkephalin processing is incomplete in the neonatal rat adrenal medulla and have postulated that immaturity of either the nervous input to the gland or the endocrine hypothalamus-pituitary-adrenal axis might be involved in the failure of the gland to yield free met-enkephalin. Therefore, we investigated whether cholinergic and glucocorticoid agonists may act in vivo on neonatal proenkephalin processing; reserpine, a strong activator of precursor cleavage, was also tested. Acute administration of nicotine, pilocarpine and reserpine to 24-hour-old rats increased the content of enkephalin-containing peptides (ECP) after 72 h (4-day-old rats) and activated the posttranslational processing of proenkephalin to high, intermediate and low molecular weight peptides respectively, although free met-en-kephalin was not produced. Chronic treatment with nicotine and pilocarpine neither modified the concentration of ECP nor were able to induce free met-enkephalin production. Chronic administration of dexamethasone increased ECP levels in the adrenal of 4-day-old rats and caused proenkephalin processing to intermediate- and low-molecular-weight products including the production of free met-enkephalin. These results indicate that only dexamethasone was able to induce the production of met-enkephalin in the adrenal of neonatal rats, suggesting an involvement of the hypothalamus-pituitary-adrenal axis in the proteolytic maturation of proenkephalin during the ontogeny of rat adrenal medulla.

ISSN:0028-3835    

DOI:10.1159/000126309

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Previous studies have shown that activation of the 5-HT1A receptor subtype enhances rat plasma ACTH concentration. Such receptors have been suggested to be located on CRH neuronal cell bodies in the paraventricular nuclei of the hypothalamus (PVN). In this report, microinjection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT1A agonist, into the PVN increased rat plasma ACTH concentration in a dose-related manner. Similar responses were observed when two other 5-HT1A agonists, buspirone and gepirone, were used. (± )-Pindolol, known to have 5-HT1A antagonist properties, blocked the effect induced by an optimal dose of 8-OH-DPAT after injection into the PVN. This same dose of 8-OH-DPAT also induced a decrease of hypothalamic CRH concentration, which was completely antagonized as well by pretreatment injection of ( ± )-pindolol into the PVN. A significant inverse correlation was found between hypothalamic CRH and plasma ACTH levels. These results confirm that elevation of the plasma ACTH concentration induced by 5-HT1A receptor subtype activation is mediated by the release of CRH from the paraventricular nuclei of the hypothalamus in rats, but do not exclude other mechanism

ISSN:0028-3835    

DOI:10.1159/000126332

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Section of the neurohypophyseal stalk classically produces a triphasic response: diabetes insipidus (1st phase), hyponatremia or normonatremia (2nd phase), and diabetes insipidus (3rd phase). Transient hyponatremia without diabetes insipidus has been reported after transsphenoidal pituitary surgery. We report two additional cases of transient hyponatremia which occurred 6-8 days after pituitary surgery. We hypothesize that this outcome may be due to partial section or damage of the hypothalamiconeurohypophyseal tracts. The remaining intact vasopressin neurons function normally to protect against the diabetes insipidus of the first and third phase, but leak of vasopressin from the damaged tracts and posterior pituitary is sufficient to cause what can be described as an isolated second phase. To study this hypothesis in rats, partial damage to the hypothalamicneurohypophyseal tracts was produced by radio-frequency lesions. The lesions did not affect anterior pituitary function. A variety of responses in posterior pituitary function occurred, including classic triphasic response in 2 rats and transient hyponatremia in 20 of 35 lesioned animals. The mean sodium nadir was 128.7 ± 1.5 mEq/l in comparison to the sham-operated value of 140.0 ± 0.4 mEq/l. Of the 20 rats exhibiting transient hyponatremia, 12 went on to develop diabetes insipidus, and 8 recovered. In the recovered group, the transient hyponatremia occurred 1-3 days after lesioning and returned to normal by day 7 which corresponds to the timing of the second phase of the triphasic response in rats. Hyponatremia was accompanied by vasopressin levels inappropriate for the plasma sodium level, inappropriately concentrated urine, water retention, and natriuresis. Animals that recovered from hyponatremia had sufficient vasopressin function to maintain normal plasma sodium with normal levels of fluid intake and were able to tolerate 30 h of fluid deprivation with minimal dehydration and elevation of plasma sodium. However, in this group, the vasopressin release in response to hypertonic saline infusion was attenuated. At sacrifice immunohistochemistry of neurophysin was performed, and a portion of the hypothalamiconeurohypophyseal tract in the internal zone of the median eminence was found to be intact in all animals which recovered, i.e., there was partial section. Thus, in both the patients and in the animals, the transient hyponatremia had the characteristic etiology, timing, and duration of an isolated second phase of the triphasic respons

ISSN:0028-3835    

DOI:10.1159/000126310

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In the ewe, estradiol and progesterone inhibit luteinizing hormone (LH) secretion during the breeding season. Endogenous opioid peptides (EOP) are also inhibitory to LH secretion, and both estrogen and progesterone have been reported to enhance EOP inhibition of LH release. Which EOP are involved in this inhibition is unclear. In this study, we concentrated on β-endorphin because evidence for its ability to inhibit LH secretion exists in ewes. We first studied the distribution of β-endorphin-immunoreactive neurons in 4 cycling ewes using immunocytochemistry. Cell bodies were found only within the medial basal hypothalamus (MBH) and were concentrated in arcuate nucleus and mammillary recess of the third ventricle, with a few in the median eminence. Extensive fiber tracts were seen in preoptic area (POA) and median eminence. We next tested the hypothesis that gonadal steroids increase the synthesis of EOP by measuring levels of mRNA for proopiomelanocortin (POMC), the precursor to β-endorphin. Ovariectomized ewes were treated with no steroids (n = 7) or given subcutaneous Silastic implants containing either estradiol (n = 6) or progesterone (n = 6). After 4 days of treatment, EOP inhibition of LH secretion was measured by determining the LH response to WIN 44,441-3 (WIN), an EOP antagonist. LH pulse frequency and pulse amplitude were determined in blood samples collected at 12-min intervals for 3 h before and after intravenous administration of 12.5 mg WIN. WIN injection increased (p < 0.01) the LH pulse frequency only in progesterone-treated and pulse amplitude only in estradiol-treated ewes. After blood sampling, the ewes were killed, and POA, MBH, and pituitary gland were removed. Total RNA was extracted from these tissues and dot blotted onto nitrocellulose membranes for hybridization with a DNA probe complementary to the POMC mRNA. The resulting autoradiographs were quantified densitometrically. Levels of POMC mRNA in the MBH were increased (p < 0.01) by both estradiol and progesterone as compared with the no steroid group. There was no detectable POMC mRNA in the POA. These results suggest that estrogen and progesterone enhance EOP inhibition of LH secretion by increasing POMC mRNA levels and thus synthesis of β-endorp

ISSN:0028-3835    

DOI:10.1159/000126311

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The sheep exhibits a marked sex difference in the timing of the pubertal increase in luteinizing hormone (LH). Male lambs undergo a reduction in sensitivity to inhibitory steroid feedback, leading to an increase in LH by 10 weeks of age, but females remain hypersensitive until 30 weeks of age. Endogenous opioids suppress LH secretion in the female lamb prepubertally and in adult male and female sheep. It has been suggested that a reduction in opioid inhibition of LH secretion is the signal to time puberty. Therefore, if a decrease in opioid tone occurs during sexual maturation, it should begin earlier in the male lamb than in the female. The objective of this study was to compare opioid inhibition of LH secretion in male and female lambs in relation to the timing of puberty. Our approach was to examine the response to the opioid antagonist naloxone at various ages in both sexes. To determine the timing of the pubertal LH rise in the presence of constant inhibitory steroid feedback, male and female lambs (n = 5 each) were gonadectomized at 3 weeks of age and implanted with a Silastic capsule of estradiol. They were then challenged with naloxone at 5, 11, and 23 weeks of age; blood samples were collected every 12 min for 8 hours, and lambs received naloxone (1 mg/kg i.v.) at hours 4, 5, 6, and 7. Mean LH before and during naloxone treatment was compared at each age. During the 4-hour pretreatment period, no LH pulses were evident in prepubertal females at 5, 11, or 23 weeks of age, and mean LH remained low (0.8 ± 0.05 ng/ml). In prepubertal males, mean LH was 1.5 ± 0.2 ng/ml at 5 weeks of age and rose at puberty to 6.8 ± 0.3 ng/ml by 23 weeks of age. Despite this sex difference in the timing of the pubertal LH rise, neither male nor female lambs increased LH secretion in response to naloxone until 23 wseeks of age. At this time, mean LH in females increased by 3.2 ± 0.7 ng/ml over pretreatment values in response to naloxone and increased by 5.0 ± 0.9 ng/ml in males. Thus, although opioid tone is expressed prepubertally in the female lamb, it is not evident until after puberty in the male. In a second experiment, we determined if increasing the concentration of estradiol in circulation affects the gonadotropin response to naloxone. LH pulse frequency during naloxone treatment did not differ in ovariectomized prepubertal females bearing 3-, 10-, or 30-mm implants of estradiol, although the larger implants of estradiol suppressed LH during the pretreatment period. These data suggest that increasing steroid negative feedback does not increase opioid tone, thereby reducing the gonadotropin response to a single dose of naloxone. Together, these studies provide evidence that in sheep the timing of the pubertal rise in LH secretion is not causally related to changes in opioid inhibition; rather, other factors including age or season may influence when endogenous opioids begin to serve a major role in modulating gonadotropin secretion in this spe

ISSN:0028-3835    

DOI:10.1159/000126312

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effects of bombesin receptor antagonist RC-3095 and gastrin-releasing peptide [GRP (14–27)] on basal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels, as well as on the release of LH and FSH in response to LH-releasing hormone, were studied in normal and castrated male rats. We also examined the release of LH and FSH after intracerebroventricular injection of RC-3095 under different types of anesthesia (urethane, sodium pentobarbital, Metofane). Following injection of 10 µg RC-3095 into the lateral brain ventricle, serum LH levels were rapidly and significantly (p < 0.001) lowered. This effect lasted for at least 60 min and was not affected by the type of anesthetic used. Serum FSH levels were not affected by intracerebroventricular administration of RC-3095 or GRP (14–27), indicating different central control mechanisms between LH and FSH release. The suppressive effect of RC-3095 on LH release could be completely prevented by prior intracerebroventricular administration of GRP (14–27) at a dose of 1 µg, but intravenous administration of either peptide RC-3095 or GRP (14–27) did not change the basal levels of LH, FSH, and testosterone. The pituitary LH response to LH-releasing hormone was also not modified by intravenous administration of RC-3095. These results indicate that bombesin-like peptides might be involved in control of LH release from the pituitary by an action on the CNS which is mediated by specific bombesin

ISSN:0028-3835    

DOI:10.1159/000126313

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In this study we have examined the direct glucoregulation of prolactin secretion from normal anterior pituitary cells in vitro and have found that changes in medium glucose concentration regulate the amount of prolactin released. Nature and/or degree of this response to glucose was influenced by some effect, long-lived in vitro, which was correlatable to serum insulin levels. When the cells were derived from animals with mean low-normal serum insulin levels, there was a stimulation of prolactin secretion by hypoglycemia, the response was rapid, transient, dose-dependent, and could be duplicated by 2-deoxyglucose. When the cells were derived from animals with a higher mean serum insulin level, the prolactin secretion from the cells was slowly, adversely affected by hypoglycemia. Conversely, elevated glucose caused a depression in prolactin secretion in the first group and a stimulation of prolactin secretion in the second. We conclude (1) that modulation of glucose levels in vitro regulates prolactin release from pituitary mammotrophs and (2) that this glucose regulation of prolactin release is in turn coregulated with or regulated by insulin.

ISSN:0028-3835    

DOI:10.1159/000126314

出版商:S. Karger AG    

年代:1992

数据来源: Karger