摘要:

Progesterone and its metabolite 5α-dihydroprogesterone (5α-DHP) have been shown to bring about gonadotropin release in the estrogen-primed ovariectomized rat. One of the actions of progesterone is the decrease in occupied estrogen receptors (E2RS) in the anterior pituitary and uterus. This study attempted to determine if 5α-DHP had a similar effect on pituitary and uterine E2RS. Estrogen-primed ovariectomized mature female rats were injected with either vehicle, or 0.2, 0.8 or 2 mg/kg body weight (BW) of 5α-DHP, 2 h before sacrifice and 1 h before the last estradiol injection (2 µg/rat). Nuclear E2RS were determined by Scatchard analyses in the uterus and anterior pituitary. Total nuclear E2R levels of both tissues showed a 2-fold increase in the number of estradiol-binding sites after estradiol administration, as compared to control groups. In estradiol-primed rats, 5α-DHP produced a significant decrease in total nuclear E2R levels in a tissue-specific manner. In the pituitary, there was a maximal and significant decrease in nuclear E2RS with 0.2 and 2.0 mg/kg BW of 5α-DHP as compared to estradiol alone; the intermediate dose of 0.8 mg/kg BW of 5α-DHP induced a smaller nonsignificant change in nuclear E2RS. In the uterus, 5α-DHP showed a dose-dependent decrease in nuclear E2RS. The 5α-DHP effect in both tissues was due to a specific reduction in the occupied form of nuclear E2RS levels. The unoccupied form of E2RS was unaffected by 5α-DHP administration. 5α-DHP did not have any effect in the absence of estrogen priming. The acute tissue-specific decrease in occupied E2RS induced by 5α-DHP was similar to that previously described by us with progesterone in the same animal model. The dose of 5α-DHP required was less than the dose of progesterone for compa

ISSN:0028-3835    

DOI:10.1159/000125588

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The aim of the present study was to evaluate the changes in the diurnal rhythm of the hypothalamic β-endorphin (β-EP) contents in female rats as a function of circulating estrogens. With this purpose we evaluated the diurnal hypothalamic β-EP changes (1) during the estrous cycle, and (2) in ovariectomized rats with and without acute and chronic estrogen replacement. Ovariectomized rats were treated either acutely with 10 µg of estradiol benzoate (EB) or chronically with 2 µg/day of EB for 15 days. β-EP concentrations were measured in acid extracts of medial basal hypothalamus by a specific radioimmunoassay. During the estrous cycle, hypothalamic β-EP concentrations showed a significant nocturnal increase, with no difference between the 4 days of the cycle. On the day of estrus, β-EP concentrations between 12.00 and 18.00 h resulted significantly lower than in the other days of the cycle. After ovariectomy, the night-related changes in hypothalamic β-EP disappeared. The acute administration of EB induced a significant increase in hypothalamic β-EP after 21 h (18.00 h). On the other hand, the chronic replacement restored the nocturnal peak of hypothalamic β-EP (18.00, 21.00, 24.00 h). The present data emphasize the role of central β-EP in regulating the reproductive functions. Moreover, the effect of estrogen in modulating the circadian changes in hypothalamic β-EP supports the important role of estrogens in br

ISSN:0028-3835    

DOI:10.1159/000125589

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The effects of morphine on the frequency and duration of the characteristic bursts or ‘volleys’ of multiunit electrical activity (MUA) associated with pulsatile pituitary luteinizing hormone (LH) secretion were studied in unanesthetized ovariectomized rhesus monkeys bearing bilateral arrays of electrodes implanted in the mediobasal hypothalamus. Morphine administration resulted in a dose-dependent decrease in MUA volley duration and frequency. When morphine was infused at 10 µg/kg/h, the inhibiting effect on volley duration was observed without a change in volley frequency. It is concluded that the frequency and duration of hypothalamic MUA volleys associated with pulsatile LH secretion may be independently regul

ISSN:0028-3835    

DOI:10.1159/000125590

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

This study in the female lamb determined if photoperiod influences pulsatile LH secretion before puberty. Moreover, we reevaluated the hypothesis that the photoperiod-modulated decrease in responsiveness to ovarian steroid inhibition which results in increased pulsatile LH secretion during sexual maturation reflects an increase in direct central nervous system ‘drive’ of gonadotropin secretion. The experimental approach was to monitor pulsatile LH secretion in the presence and absence of estradiol negative feedback during development in the same individuals. This was accomplished by the periodic replacement and removal of constant-release estradiol capsules every 3 weeks in ovariectomized lambs (OVX) which were raised in photoperiods that delay or permit normal puberty. A new algorithm was used for identification of episodes of LH secretion. In OVX lambs in the permissive sequence of photoperiods (long days of 16L:8D until 18 weeks of age, followed by short days of 8L:16D), LH pulse frequency was low in the presence of estradiol early in life at 9 weeks of age, but increased at later ages. LH pulse frequency in the presence of estradiol feedback was not associated with that in the absence of estradiol replacement. LH pulse frequency was high throughout development in the absence of estradiol and increased further at the time when responsiveness to estradiol negative feedback decreased. In lambs raised in the inhibitory sequence of photoperiods (short days until 18 weeks of age followed by long days), LH pulse frequency in the presence of estradiol remained low throughout the duration of the experiment, but in the absence of estradiol, LH pulse frequency increased with age. In both groups, LH pulse frequency in the absence of estradiol was greater than in the presence of estradiol at all stages of development, but was lower in lambs in inhibitory photoperiod than in those in the permissive photoperiod at 6 weeks of age. Thus, photoperiod can modulate LH secretion even before the age of puberty, as determined in the absence of ovarian steroid feedback. Overall, this study reveals that photoperiod can modulate LH pulse frequency in the absence of estradiol negative feedback before the normal time of puberty, and that changes in photoperiod markedly influence the timing of the developmental decrease in responsiveness to estradiol negative feedback. The decrease in responsiveness to ovarian steroid feedback during the final stages of sexual maturation is not necessarily a consequence of a high hypothalamic drive on gonadotropin secretion because in lambs raised in an inhibitory sequence of photoperiods, the age-related increase in LH pulse frequency in the absence of estradiol is not accompanied by an increase in pulse frequency in the presence of estrad

ISSN:0028-3835    

DOI:10.1159/000125591

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The possible involvement of arachidonic acid (AA) release in growth-hormone-releasing factor (GRF)-induced somatostatin (SRIF) release from the median eminence (ME) of the hypothalamus was evaluated in adult male rats using an in vitro incubation system. The MEs were preincubated with [14C]-AA, then washed and incubated with vehicle or test agents, and the release of SRIF and [14C]-AA into the medium was measured. In the experiments designed only to determine SRIF release, the MEs were first preincubated for 30 min. The medium was then discarded and replaced with fresh buffer or test substances and incubated for 10, 20 and/or 30 min. GRF (10–10M) stimulated both AA and SRIF release significantly within 20 min, with maximum release occurring at 30 min. The stimulatory effect of GRF on AA release was coincident with the release of SRIF. A phospholipase A2 inhibitor (10–6M, quinacrine) completely abolished the stimulatory effect of GRF on both AA and SRIF release. The release of SRIF induced by GRF was also inhibited by both indomethacin (10–6M, a cyclooxygenase inhibitor) and metyrapone (10-6M, a cytochrome P-450 inhibitor). On the other hand, nordihydroguaiaretic acid (10–6M, a lipoxygenase inhibitor) had no effect on GRF-evoked SRIF release. The data presented here suggest that an important GRF-mediated event leading to SRIF secretion is an elevated release of AA from ME fragments in vitro. In conclusion, our data are suggestive that the stimulatory effect of GRF on SRIF release is due, in part, to the release and subsequent metabolism of AA to one or more meta

ISSN:0028-3835    

DOI:10.1159/000125592

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The activity of brain cortex-derived phosphatidylserine (BC-PS) on the neuroendocrine and neurovegetative responses to physical stress was tested in 8 healthy men who underwent three experiments with a bicycle ergometer. According to a double-blind design, before starting the exercise, each subject received intravenously, within 10 min, 50 or 75 mg of BC-PS or a volume-matched placebo diluted in 100 ml of saline. Blood samples were collected before and after the exercise for plasma epinephrine (E), norepinephrine (NE), dopamine (DA), adrenocorticotropin (ACTH), cortisol, growth hormone (GH), prolactin (PRL) and glucose determinations. Blood pressure and heart rate were also recorded. Physical stress induced a clear-cut increase in plasma E, NE, ACTH, cortisol, GH and PRL, whereas no significant change was observed in plasma DA and glucose. Pretreatment with both 50 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress.

ISSN:0028-3835    

DOI:10.1159/000125593

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The functions of tuberoinfundibular dopaminergic (ΗDA) neurons after long-term estradiol treatment were investigated in Fischer 344 (F344) rats which have high susceptibility to estradiol-induced prolactin (PRL)-secreting pituitary tumors. Dopamine synthesis in and release from TTDA neurons were determined in vitro by 3,4-dihydroxyphenylalanine (DOPA) accumulation in the median eminence following incubation with a DOPA decarboxylase inhibitor and endogenous dopamine release from the median eminence, respectively. The concentration of serum PRL and the weight of the anterior pituitary in ovariectomized F344 rats were markedly increased 3 weeks after a single injecction of 2 mg estradiol valerate (EV) and decreased thereafter, but still showed higher levels at 15 and 24 weeks than control ovariectomized rats. Dopamine contents in the median eminence were decreased 3 weeks and unchanged 24 weeks after EV treatment. DOPA accumulation and basal dopamine release in the median eminence of F344 rats were decreased 3 weeks and increased 15 and 24 weeks after EV treatment, similarly to those of Wistar rats as reported previously. However, EV treatment, which caused similar increases in the concentrations of serum PRL and estradiol in F344 and Wistar rats, decreased KCl-induced dopamine release in Wistar rats at 3 weeks, but failed to do so in F344 rats. KC1-induced dopamine release 24 weeks after a single EV injection in F344 rats was greater than that in control rats, whereas the dopamine release 24 weeks after the last treatment of 4 injections at 3-week intervals was not different from that in control rats. Sustained high levels of serum PRL for 3 weeks achieved by pituitary transplants under the kidney capsule increased basal and KCl-induced dopamine release in F344 rats. These results suggest that (1) estradiol is less effective in inhibiting KCl-induced release of dopamine from ΗDA neurons in F344 rats, and (2) extension of the period of estradiol treatment suppresses the enhancement of ΗDA function by estradiol withdraw

ISSN:0028-3835    

DOI:10.1159/000125594

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The regulation of dopamine accumulation in cultured rat hypothalamic cells by adenosine 3’,5’-cyclic monophosphate (cAMP) was investigated in cultures of newborn rat hypothalamic cells. Both dibutyryl cAMP, (Bu)2-cAMP, and forskolin enhanced [3H]dopamine accumulation in a dose-dependent manner. cAMP also enhanced [3H]dopamine accumulation, but to a lesser degree. Neither n-butyrate nor adenosine alone enhanced [3H]dopamine accumulation. (Bu)2-cAMP had no effect on basal efflux of [3H]radioactivity. The effect of (Bu)2-cAMP appeared on day 5 of culture, reached a maximum on day 6, and then rapidly decreased. These results suggest that dopamine uptake by cultured rat hypothalamic cells is regulated by intracellular c

ISSN:0028-3835    

DOI:10.1159/000125595

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

The changing roles of the hypothalamus and pituitary in regulating thyroid hormone levels in the rat during ontogeny has not been fully elucidated. It has been reported that endogenous TRH begins to stimulate TSH secretion at 5–8 days after birth but that the pituitary responds to hypothyroidism during late gestation. To determine the onset and extent of TRH response to low thyroid hormone levels during ontogeny, normal and hypothyroid rats treated with methimazole for 7 days were sacrificed at 16 days gestation (E16), 20 days gestation (E20), 7, 21 and 56 days after birth (n = 5/study group). Plasma hormones were assayed from pregnant mothers, pups (pooled) and adults. Levels of TRH mRNA were measured in the paraventricular nuclei (PVN) by in situ hybridization histochemistry. A labeled 48-base cDNA oligonucleotide for TRH was hybridized with brain slices (n = 6/animal) in the region of the medial parvocellular division of the PVN of the hypothalamus and the signal was quantitated by digitized computer analysis. Plasma-free T4 levels decreased and plasma TSH levels increased in the animals treated with methimazole as compared to the euthyroid controls. TRH mRNA was detected in the PVN at E16 after brain slices were dipped in emulsion and granules observed by dark-field microscopy. In the euthyroid animals, TRH mRNA increased from E20 (150 ± 9 OD units) to 7 days (222 ± 5 OD units) and remained unchanged at 21 days (252 ± 27 OD units) and 56 days (244 ± 6 OD units). The hypothyroid rats as compared to age-matched controls, had TRH mRNA levels that were unchanged at E16 and E20 and increased to 121% at 7 days (269 ± 9 0D units; p < 0.001), 176% at 21 days (461 ± 26 OD units; p < 0.001), and 225% at 56 days (545 ± 20 OD units; p < 0.001). In summary, TRH mRNA was present in the PVN at E16 and increased until 7 days after birth. TRH mRNA was not altered with hypothyroidism until after E20 and prior to or on the 7th day after birth when levels increased in response to low thyroid hormone levels. Thus, the ontogeny of the regulation of thyroid hormone feedback on TRH mRNA levels and of TSH secretion by endogenous TRH may be temporally associated suggesting an important role of PVN maturation in the development of the thyr

ISSN:0028-3835    

DOI:10.1159/000125596

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Intracellular recordings were made from hypothalamic arcuate (ARC) neurons with biocytin-filled electrodes under current- and voltage-clamp in slices prepared from ovariectomized guinea pigs which were pretreated with estradiol. Forty-three neurons were identified after linking the intracellular biocytin with streptavidin-FΓΓC and subsequently were examined for β-endorphin immunoreactivity. Ten of these neurons were immunoreactive for β-endorphin. β-Endorphin neurons displayed the following passive membrane properties: RMP: –56 ± 2 mV; Rin: 439 ± 66 MΩ; τ: 17.5 ± 2.4 ms; and often fired spontaneously (5.9 ± 2.2 Hz). These membrane characteristics were not different from identified neurons in the ARC that were not immunoreactive for β-endorphin. β-Endorphin neurons exhibited instantaneous inward rectification and time-dependent rectification. The µ-opioid agonist Tyr-ö-Ala-Gly-MePhe-Gly-ol (DAGO) decreased spontaneous firing, induced membrane hyperpolarization (12 ± 2 mV; range 6–22 mV) and decreased the Rin (38 ± 4%) of the β-endorphin neurons. These effects of DAGO were blocked by the opioid antagonist naloxone (1 µM) and were not blocked by 1 µM TTX. DAGO-responsive cells were unaffected by either ĸ- or δ-receptor opioid agonists. These results indicate that µ-receptors may be autoreceptors on ARC β-endorphin neurons and that activation of opioid µ-receptors hyperpolarizes β-endorphin neurons via an increase in K+ conductance. Therefore, opioid peptides may modulate opioid tone through an ‘ultra-short l

ISSN:0028-3835    

DOI:10.1159/000125597

出版商:S. Karger AG    

年代:1990

数据来源: Karger