摘要:

We have investigated putative dopaminergic regulation of opiomelanotropinergic activity in the arcuate/periarcuate mediobasohypothalamus (MBH) by assessing the changes in MBH tyrosine hydroxylase (TH; rate-limiting enzyme in catecholamine synthesis) and proopiomelanocortin (POMC; opiomelanotropin precursor) mRNA levels under conditions in which endogenous tuberoinfundibular dopaminergic activity exhibits marked changes. Adult Sprague-Dawley rats were sacrificed at 09.00 and 15.00 h, and individual MBH POMC and TH cytoplasmic mRNA levels were simultaneously quantified by multiplex solution hybridization-RNase protection assay with protected fragments separated by polyacrylamide gel electrophoresis. In ovariectomized (OVX) rats treated for 3 days with low-dose estradiol (E2) implants (resulting in 18 ± 4 pg E2/ml serum), the MBH levels of POMC and TH mRNAs were approximately 17 and 31% lower than those measured in OVX controls, respectively. In OVX rats implanted for 20 days with larger E2 implants (99 ± 9 pg E2/ml serum), POMC and TH mRNA levels were approximately 29 and 41% lower than in OVX controls, respectively. Additional groups were exposed to the higher E2 dose for 20 days and then killed 10 or 20 days after removal of the E2 implant. In these rats, POMC mRNA levels rebounded to the same level seen in OVX controls, while TH mRNA levels even exceeded control values by 22–27%. TH and POMC mRNA levels did not change significantly between 09.00 and 15.00 h, except 10 days after removal of the E2 implants, when 09.00 h POMC mRNA levels were higher than the 15.00 h levels. MBH POMC and TH mRNA levels were positively correlated with each other within individual animals. This correlation is maintained when both POMC and TH mRNA levels are suppressed in response to both 3-day low-dose and 20-day high-dose E2 treatment. However, although rat MBH opiomelanotropinergic and tuberoinfundibular dopaminergic mRNA biosynthesis thus appear to be positively correlated, the coregulation or functional interactions of these two neuronal systems remain to be determi

ISSN:0028-3835    

DOI:10.1159/000126241

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Previous studies indicate that 7 days after testicular administration of naloxone, serum testosterone (T) concentration and basal T secretion in vitro decrease significantly. In neonatal rats, short-term (2 h) intratesticular treatment with 0.3 µg (D-Met2-Pro5)-enkephalinamide suppresses steroidogenesis. In the present study, testicular treatment with naloxone or enkephalinamide was combined with hemivasectomy (which also includes transection of the inferior spermatic nerve). When local treatment with naloxone was combined with vasectomy in 15-day-old rats, the opioid antagonist-induced increase in testicular weight, the decrease in basal T secretion of the treated gonad and the drop in serum T level could not be observed 7 days postsurgery, despite the fact that in immature rats, hemivasectomy, by itself, also reduces steroid secretion. Similarly, in 5-day-old animals, the short-term (2 h) effect of testicular enkephalinamide on T secretion was prevented by vasectomy. These data suggest that local testicular actions exerted by endogenous opioid peptides might be modulated by the inferior spermatic nerve

ISSN:0028-3835    

DOI:10.1159/000126242

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Pituitary tumorigenesis occurs in a transgenic line of mice, α-T7, which carries a hybrid transgene composed of the 5’ flanking region of the human glycoprotein hormone α-subunit gene (1.8 kb) linked to the coding region of the SV40 T-antigen gene (α-Tag). Tumor foci were identified within the anterior pituitary of both male and female transgenic mice. In addition to a parenchyma with hypertrophied endocrine cells, mostly of the gonadotrope lineage, we here report the unexpected presence of neural tissue within the anterior pituitary, either as foci as large as 1.0 mm in diameter or greater, or in delicate bundles ramifying amongst the granulated parenchymal cells. Areas richest in neural tissue frequently were associated with tumor tissue composed of giant cells of three varieties, all with electron-lucent cytoplasm and similar organellar distribution including small secretory granules (80–160 nm diameter). In type I cells, the secretory granules were aligned at the plasma membrane; in type II cells, the secretory granules were distributed throughout the cytoplasm; type III cells formed colloid-filled follicles and their secretory granules rarely exceeded 100 nm diameter. These giant cells frequently had bizarre pleomorphic nuclei intensely immunopositive for T-antigen and cytoplasm which was lightly immunopositive for α-subunit, and immunopositive either for the LH-β or TSH-β subunits. Neural tissue contacted the normal granulated parenchymal cells directly, i.e., without a basal lamina or any connective tissue intervening, but only rarely formed synaptoid junctions with these granulated cells. Synaptoid junctions containing round, smooth vesicles, as well as dense core vesicles, were numerous between the neural processes themselves and between the neural tissue and the giant cells of the tumor tissue. These data suggest that in α-T7 transgenic mice the giant cells represent highly transformed gonadotropes or thyrotropes, and that a neurotrophic factor may be expressed by these transformed pituitary parench

ISSN:0028-3835    

DOI:10.1159/000126243

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In order to determine whether cortisol acts directly at the level of the fetal pituitary to promote pars distalis corticotroph maturation, we have infused cortisol into the hypothalamo-pituitary-disconnected (HPD) fetal sheep from 111 to 117 days of gestation. In this study we have measured fetal plasma cortisol and immunoreactive adrenocorticotrophic hormone (ir-ACTH) concentrations between 105 and 116 days of gestation, and we have determined the proportions of adult- and fetal-type corticotrophs in the pars distalis of catheter control fetuses and in HPD fetuses infused with either saline (HPD + SAL) or cortisol (2 mg/day; HPD + F). The fetal plasma cortisol concentrations did not change significantly following HPD. The mean fetal plasma cortisol concentration between 113 and 116 days was threefold higher in the HPD + F fetuses than that measured in HPD fetuses. Following HPD, fetal plasma ir-ACTH concentrations were significantly higher than in catheter control fetuses. Despite the significant elevation in plasma cortisol concentrations in HPD + F fetuses between 113 and 116 days, plasma ir-ACTH concentrations were not different in these fetuses from HPD fetuses infused with saline. At 117 days of gestation in HPD + F fetuses, the proportion of fetal-type corticotrophs in the pars distalis was significantly less than in the HPD + SAL fetuses; however, there was no significant change in the proportion of adult-type corticotrophs in the pars distalis following cortisol infusion. We have shown that cortisol has a direct trophic effect on the maturation of the pars distalis corticotrophs; however, the full maturation of these cells requires an intact hypothalamo-pituitary axis. These findings demonstrate the importance of the fetal hypothalamus in anterior pituitary corticotroph maturation during the last third of gestation.

ISSN:0028-3835    

DOI:10.1159/000126244

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The dynamics of pro-opiomelanocortin (POMC) biosynthesis in the adult rat are altered by demands imposed on the system, such that acute stress increases in the efficiency of anterior pituitary (AP) posttranslational events, while repeated stress increases pretranslational events. In contrast, the developing animal has a limited adrenocortical response to acute stress during the first 2 weeks of life (stress nonresponsive period). In this study, we investigated how the maturing AP and intermediate lobe (IL) POMC cells respond to repeated demand. Measurements of AP and IL POMC mRNA and POMC peptides were performed using Northern gels and radioimmunoassay, respectively. Plasma ACTH and corticosterone measurements were also performed. Maternal isolation, for 1 h on 3 consecutive days, was used as a repeated stress stimulus. The developing AP and IL exhibit an age-related increase in POMC mRNA and peptide levels. On the other hand, AP and IL do not respond to repeated intermittent maternal isolation during the first 2 weeks of life. However, a significant corticosterone release is seen in the 14 and 21-day-old animals. A change in POMC mRNA level is only detected in the 21-day-old AP where levels decrease. Therefore, an adrenocortical response to repeated intermittent maternal isolation predates the appearance of glucocorticoid inhibition of POMC expression in the 21-day-old animal. We propose that an immature neuronal inhibitory circuit during the 3rd week of life causes a sustained corticosteroid response which may in turn trigger AP-delayed feedback.

ISSN:0028-3835    

DOI:10.1159/000126245

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The possible role of neuropeptide Y (NPY) in mediating the relationship between pituitary LH secretion and growth retardation due to restricted feeding was examined in ovariectomized (OVX) prepubertal ewe lambs. One specific objective examined whether there was an inverse relationship between concentrations of NPY in four diencephalic brain regions and pituitary LH secretion in ewe lambs 29-30 weeks old which had been growth retarded since 8 weeks and OVX at 24 weeks. Through dietary restriction, body weight was held constant at 20.7 ± 0.5 kg in 13 growth-retarded ewes as compared with 48.0 ± 0.6 kg for 5 age-matched control ewes at 29-30 weeks of age. Episodic LH was quantified at 10-min intervals for 190 min/day on 3 of the 8 days immediately before euthanasia. Serum LH averaged 6.5 ± 0.6 ng/ml in control ewes with a mean pulse frequency of 1.0 ± 0.1 pulses/h. Serum LH in growth-retarded ewes was much less episodic (0.2 ± 0.05 pulses/h) and averaged only 1.2 ± 0.2 ng/ml. All ewes were euthanized during week 30, and the following brain regions were dissected: basal forebrain, preoptic area, median eminence and remainder of hypothalamus. Following extraction, NPY concentrations (pg/mg of original tissue) were quantified by radioimmunoassay. In each brain region, NPY concentrations were greater (p < 0.05) in 6 growth-retarded ewes than in 5 control ewes (median eminence: 5.2 vs. 0.6; remainder of hypothalamus: 3.3 vs. 0.8; preoptic area: 3.1 vs. 0.8, and basal forebrain: 2.2 vs. 1.2). A secondary objective examined whether the LH and NPY parameters were rapidly altered by transient changes in feed consumption. Therefore, a subgroup of 7 growth-retarded ewes was given access to increased feed during the last week of the experiment (denoted as refed growth-retarded), but feed consumption and weight gain were highly variable as only 1 ewe maintained her initially increased feed consumption for the entire 7 days. Secretion of LH as reflected in mean concentrations (2.1 ± 0.5 ng/ml) and pulse frequency (0.4 ± 0.1 pulses/h) was slightly increased (p < 0.05) in refed ewes. However, NPY concentrations (median eminence: 6.6; remainder of hypothalamus: 3.6; preoptic area: 3.6, and basal forebrain: 2.5) in the 7 refed growth-retarded ewes were similar to those of the 6 growth-retarded ewes which were not refed. Among individual refed growth-retarded ewes, there was no clear relationship among weight gain/feed consumption and hypothalamic NPY. In summary, steroid-independent suppression of LH secretion in chronically growth-retarded ewes was inversely related to elevated levels of NPY in median eminence and other diencephalic regions. Increased food availability forpnly 7 days reversed only slightly the suppression of LH and did not affect the elevated levels of hypothalamic NPY. Except for these divergent changes in refed ewes, the main results of this study are consistent with the hypothesis that increased neural production of NPY contributed to suppression of LH release in growth-retarded O

ISSN:0028-3835    

DOI:10.1159/000126246

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The hypothalamus has the highest concentration of proglucagon-derived peptides (Pgdp’s) in the brain, however, the control of the synthesis and secretion of these peptides is not understood. The goal of our studies was to examine in detail the regulation of synthesis and secretion of Pgdp’s in the hypothalamus. Hypothalamic cultures were prepared from fetal rats on day 19–21 of gestation and Pgdp’s in media and cells were determined by radioimmunoassay after treatment with test agents. Dibutyryl cyclic AMP or forskolin, activators of protein kinase A, markedly stimulated both Pgdp synthesis (by 5-fold) and secretion (by 10-fold) after 24 h of treatment (p < 0.05). The effects of protein kinase A stimulation on Pgdp’s in the hypothalamus were greater than seen in our previous studies with the Pgdp-producing pancreatic A and intestinal L cells. Therefore there are tissue-specific differences with regard to the magnitude of the response of Pgdp’s to protein kinase A stimulation. Consistent with an involvement of protein kinase A in hypothalamic Pgdp synthesis and secretion, somatostatin-14, an inhibitor of protein kinase A, was found to inhibit Pgdp synthesis and secretion in a dose-dependent fashion (p < 0.05). Phorbol myristate acetate (PMA), a stimulator of protein kinase C, did not significantly affect the synthesis or secretion of Pgdp’s at 6 h, but significantly stimulated Pgdp secretion after 24 h (p 0.05). In conclusion, our studies have shown both similarities and differences in the regulation of Pgdp synthesis and secretion by protein kinase A and C in the hypothalamus, as compared to the pancreatic A and inte

ISSN:0028-3835    

DOI:10.1159/000126247

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Effects of starvation on thyroid function were studied in 5- to 6-week-old (R× U) F1 rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T4 and T3 levels decreased, whereas the dialysable T4 fraction increased during starvation. Free T4 (FT4) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 ml KC1 increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release

ISSN:0028-3835    

DOI:10.1159/000126248

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/ 5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HTthrough the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with/7-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HTturnover.

ISSN:0028-3835    

DOI:10.1159/000126249

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In female rat age-related reproductive decline is accompanied by progressive impairment of the neuroendocrine mechanisms that regulate LH secretion. The biosynthetic activity of the pineal gland is markedly depressed and the nocturnal secretion of melatonin decreases significantly. The aim of the present study was to evaluate whether the nocturnal administration of melatonin via the drinking water (0.4 µg/ml) throughout the course of aging from 14 to 24 months of age could (1) influence the age-related changes that occur in basal serum levels of LH and in the LH response to GnRH or to naloxone stimulation at 16, 18 and 20 months of age, and (2) delay the onset of the postreproductive constant estrous-anovulatory state as evaluated by the daily recording of vaginal smears and by occurrence of polyfollicular ovaries at 24 months of age. Our results demonstrate that melatonin replacement delays the increase in LH serum levels and the decrease in LH response to GnRH that occur in 18-month-old control animals. Furthermore, they show that melatonin treatment prevents the loss of LH response to naloxone manifested in control rats between 16 and 20 months of age. Melatonin also appears to prevent the progressive increase in the monthly occurrence of estrus phases as well as to decrease the number of rats with polyfollicular ovaries at 24 months of age in comparison to control animals. These results suggest that the age-related decrease in circulating melatonin during the night may contribute to the reproductive decline of aging, and that this effect may involve the central opioid system

ISSN:0028-3835    

DOI:10.1159/000126250

出版商:S. Karger AG    

年代:1992

数据来源: Karger