摘要:

The existence of a putative central prolactin-inhibiting factor (PIF) distinct from dopamine (DA) but dependent on DA mechanisms for release has been suggested from recent animal studies. We investigated the possibility of the existence of such a PIF in man by combining the use of monoiodotyrosine (MIT), an inhibitor of central DA synthesis, domperidone, a DA receptor antagonist that does not enter the blood-brain barrier and DA itself. 6 normal volunteers underwent three sets of studies: (1) PRL stimulation test to 400 µg TRH i.v., 1 g MIT orally or 5 mg domperidone i.v., (2) peripheral DA receptor blockade study in which either domperidone, MIT or TRH was administered at 120 min during a 240-min domperidone infusion (50 µg/min) which was preceded by a 5-mg bolus dose of domperidone i.v. and, (3) DA infusion study in which MIT was administered at 120 min during a 240-min infusion of DA in a dose (0.5 µg/kg · min) known to elevate peripheral DA concentration to levels reported for pituitary portal plasma. In the PRL stimulation tests, the mean ± SE peak response was significantly greater (p< 0.002) with domperidone (3,900 ± 840 mIU/l) than with MIT (1,880 + 400 mIU/l) or TRH (2,094 ± 450 mIU/l). In the peripheral DA receptor blockade study the initial domperidone-induced PRL response was not sustained during the domperidone infusion. Neither a second dose of domperidone nor MIT administration at 120 min resulted in a significant release of PRL. TRH administration resulted in a significant rise (p < 0.01) from 2,189 ± 470 mIU/l at 120 min to 2,950 ± 590 mIU/l at 135 min indicating that intracellular PRL stores had not been totally depleted by the initial stimulus. In the DA infusion study, the PRL suppression induced by the 240 min DA infusion (from 600 ±90 to 121 ±24 mIU/l) was not significantly altered by MIT administration (from 530 ±60 to 108 ±24 mIU/l). The failure of MIT, which acts centrally to inhibit DA activity, to induce a significant release of PRL during peripheral DA receptor blockade (with domperidone) does not support the existence of a central PIF distinct from DA. This conclusion is further supported by the failure of MIT to overcome PRL suppression induced by a peripheral infusion of DA. We conclude that in man, DA is the major PIF and that these studies do not support the presence of a central DA-mediated PIF. As dopaminergic inhibition of PRL release can be entirely accounted for by the blockade of DA action outside the blood-brain barrier, DA antagonists that cross the blood-brain barrier offer no special advantages over those

ISSN:0028-3835    

DOI:10.1159/000124115

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The influence of catecholamines on growth hormone (GH) release in female goldfish was investigated by monitoring serum GH levels following injections of drugs known to alter catecholamine synthesis and neural activities. Intraperitoneal (i.p.) injection of 6-tydroxydopamine, a catecholaminergic neurotoxin, or α-methyl-p-tyrosine, a catecholamine synthesis inhibitor, decreased serum GH levels. Intraperitoneal injection of L-β-dihydroxyphenylalanine (L-dopa) increased serum GH concentrations in a dose-dependent manner. The L-dopa-induced increase in serum GH was potentiated by i.p. injection of carbidopa, which would increase the availability of L-dopa to brain tissues by blocking the peripheral conversion of L-dopa to dopamine (DA). These results suggest that L-dopa or one of its catecholamine metabolites acts centrally to increase GH release. Intraventricular (i.v.t.) injection of DA and i.p. injection of apomorphine, a DA agonist that crosses the blood-brain barrier, increased serum GH. Intraperitoneal injection of DA did not alter circulating GH levels in normal fish or fish bearing preoptic lesions that abolish an inhibitory hypothalamic influence on GH release; however, DA increased serum GH in fish which had their blood-brain barrier destroyed by sham operation procedures. These results indicate that DA acts centrally to stimulate GH secretion, possibly by inhibiting the release and/or synthesis of GH release-inhibitory factor. Serum GH concentrations were decreased in a dose-dependent manner by i.p. injection of norepinephrine (NE), whereas i.v.t. injection of NE did not alter serum GH levels. These results indicate that NE acts outside of the blood-brain barrier to decrease serum GH levels in the goldfish, possibly by directly influencing pituitary GH cells. Preliminary data suggest that an α-adrenergic mechanism stimulating GH release in the goldfish may also be present, although the level of this action is not kno

ISSN:0028-3835    

DOI:10.1159/000124116

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Using immunocytochemistry with the sensitive avidin-biotin complex method and an antibody to the β sub-unit of rat luteinizing hormone (rat LHβ) provided by the National Hormone and Pituitary Program, NIADDK, to identify gonadotrops, the presence of angiotensin II-like immunoreactivity in the gonadotrops of the anterior pituitary gland of male rats was confirmed. However, using an antibody to rat prolactin, no angiotensin Il-like immunoreactivity could be found in lactotrops. This finding is at variance with a previous report from this laboratory, in which the lactotrops were identified with an NIADDK antibody to human prolactin. The possibility that the antibodies to human prolactin cross-reacted with rat LH was therefore investigated by a noncompetitive radioimmunological binding assay. At the same dilution used in immunocytochemistry, two different NIADDK antihuman prolactin antisera displayed 49% and 24% binding of labeled rat LHβ. Similar cross reactions were demonstrated immunocytochemically. There was no cross reactivity between rat LHβ and the antibody to rat prolactin. Consequently, the staining reported to be in lactotrops in the previous study was probably in gonadotr

ISSN:0028-3835    

DOI:10.1159/000124117

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

In the present study, we have investigated the effects of intermittent dibutyryl cyclic AMP (dbcAMP, 5 × 10–8 M), butyrate (5 × 10–8 M) and forskolin (10–4 M) on immunoreactive luteinizing hormone-releasing hormone (LHRH) release from superfused hypothalamic fragments from intact male rats of age 25, 30, 45, or 60–75 day (adult). The results indicate that at 25 days of age, male rat hypothalami were most responsive to cyclic AMP (162% of preinfusion basal LHRH release); by 30 days of age, dbcAMP also elicited increased LHRH release (120% of basal). By 45 days of age, the dbcAMP effect on in vitro LHRH release was slightly inhibitory (78% of basal); however, by adulthood, the effect of this cyclic nucleotide on LHRH release was minimal (92% of basal). Butyrate also induced age-dependent modifications in in vitro LHRH release from male rat hypothalami, with slight increases following butyrate delivery at 25 days of age (115%), slight decreases at 30 (82%) and 45 days of age (68%), and little change in adulthood (94%). This latter finding emphasizes the importance of using butyrate as a control for butyryl derivatives of cyclic AMP, which are known to liberate butyric acid as a product of hydrolysis of parent compounds. To address the possibility that the lack of effectiveness of dbcAMP in the older animal preparations was solely due to an increasing sensitivity of male rat medio-basal hypothalamus fragments to butyrate, we examined the effect of forskolin (10–4 M), an adenylate cyclase stimulator, on LHRH release. In the 30-day-old male rat preparation, continuous infusion of forskolin evoked marked increases in LHRH release, characterized by episodic surges; in contrast, this compound was relatively ineffective in inducing LHRH surges in the adult male rat condition. This study also shows that while hypothalamic LHRH concentration reached maximal levels by 45 days of age, spontaneous in vitro release of LHRH increased in a near-linear fashion as a function of age of male rat donor (from 25 days of age to adult), thus indicating a dissociation between spontaneous LHRH neuronal activity and dbcAMP-stimulated LHRH release. In sum, it can be concluded that the responsivity of the hypothalamic neural LHRH apparatus to cyclic AMP (either exogenously applied or generated through stimulation of adenylate cyclase) decreases as the rats mature, with no response close to puberty and during adulthood. In addition, maturational changes in LHRH release and LHRH concentration in superfused medio-basal hypothalamus fragments from intact male rats can be inferred using this in vitro superfu

ISSN:0028-3835    

DOI:10.1159/000124118

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The effect of Ca2+ on the biochemical characteristics of muscarinic receptors in the adenohypophysis of male and female rats at the various stages of the estrous cycle was investigated in binding experiments using the specific muscarinic antagonist N-methyl-4-piperidyl benzylate ([3H]-4NMPB) and the muscarinic agonist oxotremorine. By using Ca2+ chelators such as EGTA, and Ca2+ channel blockers such as D-600, we showed that Ca2+ profoundly alters the binding characteristics of both antagonists and agonists to the muscarinic receptors. In female rats the effect of Ca2+ on antagonist binding is mainly on the maximal binding capacity of the receptors, while changes in the dissociation constants are much more moderate. The effect is expressed in the ability of Ca2+ to expose or to eliminate binding sites as a function of the estrous cycle. In agonist binding, the presence of Ca2+ has a pronounced effect on the proportion of high-affinity binding sites, which parallels the changes induced in antagonist binding throughout the estrous cycle. Interestingly, the natural progression of the cycle from diestrus 2 to the estrous stage undergoes a change identical to that occurring in vitro upon Ca2+ removal. D-600 can completely block the effect of Ca2+ on the binding of both [3H]-4NMPB and oxotremorine. The concentration of D-600 required in order to induce such blocking is also dependent on the estrous cycle. It appears that the progression of the estrous cycle is accompanied by changes in the muscarinic receptors which may in turn be coupled to Ca2+ channels.

ISSN:0028-3835    

DOI:10.1159/000124119

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The effect of intravertebral infusion of angiotensin II on cardiac vagal efferent activity was studied in anesthetized mongrel dogs. Unilateral infusion of doses of angiotensin II as low as 5 ng/kg/min inhibited basal vagal tone and also decreased the slope of the relationship between cardiac vagal efferent activity and systolic blood pressure. Intravenous and intracarotid infusion of similar doses of angiotensin II produced little or no inhibition of vagal tone. These results demonstrate directly that angiotensin II can act centrally to inhibit cardiac vagal efferent activity and provide additional evidence that the increase in blood pressure produced by intravertebral angiotensin II results, at least in part, from decreased vagal tone to the heart.

ISSN:0028-3835    

DOI:10.1159/000124120

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The purpose of the present investigation was to determine the effects of naloxone on LHRH and catecholamine release from preoptic area-medial basal hypothalamic (POA-MBH) fragments in vitro. Ovariectomized rats were treated with estradiol benzoate, followed 2 days later by progesterone. The rats were killed 2 after progesterone administration and the POA-MBH dissected out and incubated in a perifusion system. After preincubation, medium with or without naloxone (1 mg/ml) was infused into the perifusion chambers and LHRH, norepinephrine, epinephrine and dopamine release were monitored. Naloxone concurrently released LHRH and the three catecholamines during the entire perifusion period. LHRH and catecholamine output returned to the control range within 30–45 min after cessation of naloxone infusion. These data show that naloxone can promptly stimulate catecholamine release and concur with the view that LH release evoked by naloxone in vivo may be due to hypersecretion of LHRH and they further raise the possibility that norepinephrine and epinephrine released in the vicinity of peptidergic neurons in the POA-MBH may participate in LHRH hypersecretio

ISSN:0028-3835    

DOI:10.1159/000124121

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

Recently we reported that the anteroventral periventricular nucleus (AVPv) of the preoptic region contains a dramatic sexual dimorphism in the distribution of tyrosine hydroxylase- (TH-)immunoreactive cells and fibers in the rat. This sexual dimorphism appears to be due to a greater density of dopaminergic fibers, and a larger number of dopaminergic cell bodies, in the AVPv of the female. In the present study we used an indirect immunohistochemical method to evaluate the distribution of TH-immunoreactive cell bodies and fibers, and of dopamine-β-hydroxylase-(DBH-)stained fibers, in the AVPv of female rats that were treated with testosterone propionate (TP) perinatally or postnatally, or were left untreated. All of the postnatally TP-treated animals failed to show a phasic pattern of luteinizing hormone (LH) secretion in response to estrogen and progesterone injections. Both the perinatally and postnatally TP-treated females had polyfollicular ovaries that lacked corpora lutea at the time of gonadectomy. Perinatal TP exposure resulted in what appears to be a complete masculinization of both the number of TH-stained cells and the density of TH-stained fibers in the AVPv. The number of TH-stained cells in the postnatally TP-treated females was also completely masculinized, although the density of TH-stained fibers did not appear to be altered significantly. Gonadectomy resulted in a moderate increase in the density of TH-stained fibers in adult males, and did not significantly affect the fiber density in females, or the number of TH-stained cells in either sex. The distribution of DBH-stained fibers in the AVPv did not appear to be altered in any of the treatment groups. These results suggest that the distribution of dopaminergic fibers in the AVPv may be sensitive to testosterone levels in the adult male, and that although the critical period for the development of this fiber distribution may begin in the prenatal period, the number of dopaminergic cells in the AVPv can be completely sex reversed by a single postnatal dose of TP that appears to correlate with a permanent disruption of the normal pattern of gonadotropin secretion

ISSN:0028-3835    

DOI:10.1159/000124122

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

The timing of the critical period and LH surge during the afternoon of proestrus was unchanged in female rats with degenerated retinal photoreceptors (Hunter and Royal College of Surgeons strains), when compared to female rats with intact retinae (Piebald Virol Glaxo and Wistar strains). Both RCS and Wistar strains responded to constant light (LL) exposure by attaining persistent vaginal cornification at the same rate. In addition, both RCS and Wistar strains regained normal estrous cycles when moved from LL to control lighting (LD). Therefore, an intact retinal photoreceptor layer is not essential for normal ovulatory function. In addition, these results show that the effects of LL on gonadotrophin secretion are mediated through the brain and are not the result of retinal degeneration. Measurements of retinal concentrations of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (Dopac), in Wistar and RCS rats showed that concentrations of both compounds were reduced by LL, and then increased back to control values when animals were moved back into LD. Although the magnitude of the changes in retinal concentrations of DA and Dopac was greater in Wistar than in RCS rats (possibly related to the degeneration which occurs in Wistar but not RCS rats), these results suggest that dopaminergic cells, probably within the amacrine cell population of the retina, respond to different light regimes, perhaps by changes in activity.

ISSN:0028-3835    

DOI:10.1159/000124123

出版商:S. Karger AG    

年代:1985

数据来源: Karger

摘要:

One tenable hypothesis for the etiology of the development of prolactin-secreting adenomas is that a decrease in inhibitory dopaminergic regulation leads to increased lactotroph proliferation. Dopamine receptors have been repeatedly characterized on prolactin-secreting adenomas using labelled antagonists as ligands; however, no data are available on characterization of the receptor with a dopaminergic agonist. An agonist was utilized as the radioligand in the present study to permit the direct comparison of the pharmacological characteristics of the binding site with the biological response, the inhibition of prolactin secretion. This comparison has never been reported in tissues from the same species. Binding of the dopamine agonist and α-adrenergic antagonist [3H]-dihydroergocryptine ([3H]-DHE) to particulate fractions of surgically resected human prolactin-secreting adenomas was high affinity, monophasic, and saturable. Careful characterization of the [3H]-DHE binding by competitions with a large number of dopaminergic and α-adrenergic agents revealed the presence of both dopaminergic and α-adrenergic binding sites. The presence of a saturable, high affinity α-adrenergic binding site was confirmed with the specific α-adrenergic antagonist [3H]-WB4101 as a radioligand. Although the rank order of potency for dopaminergic compounds to compete for [3H]-DHE binding was consistent with an interaction with a dopamine receptor, the inhibitory constants (Ki) calculated from the competitions were higher than expected at an anterior pituitary dopamine receptor. This appeared to be due to the lower affinity of these agents at the α-adrenergic sites. The observed potency of dopaminergic compounds was inversely related to the number of α-adrenergic sites. The concentration of [3H]-DHE necessary to occupy half of the dopamine receptors (0.75 nM) on the particulate fractions was in close agreement with the amount of this compound which inhibits 50% of the suppressible prolactin secretion from cultured adenomas (0.35 nM). We conclude that prolactin-secreting adenomas contain a high affinity dopamine receptor which interacts with both agonists and antagonists in a similar fashion as reported for the anterior pituitary of several species. Atypically these tumors contain relatively large numbers of α-adrenergic sites which do not appear to be involved in the regulation of prolactin se

ISSN:0028-3835    

DOI:10.1159/000124124

出版商:S. Karger AG    

年代:1985

数据来源: Karger