摘要:

In order to determine whether there is an abnormality in the pituitary responsiveness to GRF in the diabetic rat, we examined the in vivo and in vitro effects of hGRF-44 NH2 (hGRF) on growth hormone (GH) release in the spontaneously diabetic BB Wistar rat. Under pentobarbital anesthesia, hGRF was injected intravenously at a dose of 500 ng/kg in male diabetic BB Wistar rats (n = 11) and in male control Wistar rats matched for weight (n = 11). Basal serum GH concentrations were significantly lower in the diabetic group, (123 ± 5 ng/ml, mean ± SEM) than in the control group (362 ± 15 ng/ml). However, the GH response to hGRF was significantly greater in the diabetic group (GH increment 873 ± 153 ng/ml) than in the control group (268 ± 91 ng/ml). The effect of hGRF was further tested in a perifusion system of freshly dispersed anterior pituitary cells of diabetic BB Wistar rats and control Wistar rats. Basal secretion rate of GH from cells of diabetic rats (0.85 ± 0.06 µg/2 pituitaries · 2 min) was lower than that from cells of control rats (1.60 ± 0.18 µg/2 pituitaries · 2 min). The GH response to 2-min pulses of hGRF at concentrations of 1.56, 6.25, and 25 pM with and without somatostatin 10–9 M was significantly greater in the diabetic group than in the control group. In conclusion, there is in the spontaneously diabetic rat an increased in vivo and in vitro GH responsiveness to exogenous hGRF suggesting an abnormality of GH regulation at the pit

ISSN:0028-3835    

DOI:10.1159/000124814

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Contrary to earlier views on the inability of naloxone to affect androgen variables by way of general circulation, systemically applied naloxone (2.5 mg/kg body weight, single i.p. or i.v injection) has been shown to rapidly induce (within an hour) a significant fall (–35,7% on the average) of the concentration of serum androgen (testosterone and dihydrotestosterone; (T + DHT) in peripubertal rats (51–58 days old). Such a response to the opiate antagonist was absent, however, in low-androgen prepubertal animals (37–44 days old) and in those among peripubertal rats which still showed subcritical initial levels of androgen in circulation (<1.5 ng/ml; experiments with repeated blood sampling in catheterized animals). In peripubertal rats naloxone was also shown to induce a significant decrease (–36%) in basal in vitro androgen production by testes removed 15 or 30 min following the intraperitoneal administration of the opiate antagonist. Such an inhibitory effect on basal steroidogenesis has not been observed in control multiple-dose experiments in which incubated testes from naloxone-naive rats have been directly challenged with naloxone: on the contrary, enhancing direct effects were recorded, but only with the highest concentration of naloxone tested (KM M). The possibility thus remains open that indirect inhibitory effects of injected naloxone may be operational in intact animals. Hypoprolactinemia, known to interfere in an age-dependent manner with the responsiveness of Leyding cells to luteinizing hormone (LH), may be of particular relevance: a significant fall of serum prolactin (PRL; -46%) has been regularly observed after systemic naloxone in those age groups which also responded to the opiate antagonist by a fall of circulating androgen and a decrease in basal in vitro steroidogenesis. A concomitant rise of serum LH has also been recorded after naloxone, but in all rats including the prepubertal group which did not respond with decreases of serum PRL and a

ISSN:0028-3835    

DOI:10.1159/000124815

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

There is a great deal of conflicting data regarding the issue of whether androgens influence opiate receptors in the whole male rat brain. Although Hahn and Fishman initially reported that long-term castration produced a large increase in the density of opiate-binding sites, relative to controls, no other independent group has been able to replicate these results. Recently, the former investigators reported that procedural differences could fully account for the discrepancies in the literature. Because of the importance of demonstrating a direct biochemical association between steroid- and endogenous opioid-containing neuronal elements in brain, we have reexamined the issue of whether long-term castration influences opiate receptors in whole male rat brain. To accomplish this goal, we incorporated all of the critical procedural variables which were identified by Hahn and Fishman as possible confounding variables in such studies. Our results clearly demonstrate that under identical conditions, we were unable to replicate the results of these investigators. In addition, we attempted to use other paradigms in an attempt to resolve this long-standing controversy in the literature, but these attempts were also unsuccessful. We are unable to explain our inability to replicate the results of Hahn and Fishman. However, it should be noted that at least 4 independent groups have now failed to reproduce their findings. Thus, it appears that the intrinsically attractive hypothesis that steroids influence opiate receptors cannot be addressed using whole brain analysis or relatively crude areas of brain and relatively nonspecific opiate ligands. Rather, it seems probable that this issue can only be addressed using techniques which recognize the marked regional localization of steroid effects and multiple opioid receptor subtypes in brain (e.g. autoradiography).

ISSN:0028-3835    

DOI:10.1159/000124816

出版商:S. Karger AG    

年代:1987

数据来源: Karger

ISSN:0028-3835    

DOI:10.1159/000124817

出版商:S. Karger AG    

年代:1987

数据来源: Karger