Testosterone does not influence opiate binding sites in the male rat brain

Cicero, Theodore J.; Newman, Karin S.; Meyer, Edward R.

doi:10.1016/0024-3205(83)90003-6

Cited by 43 publications

(26 citation statements)

References 13 publications

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“…The apparent inability of M to reduce LH secre tion at 2 weeks of castration would suggest a T requirement for this effect of M. Early studies suggested that gonadal steroids may modify brain opiate receptors [11], but these results have been disputed [6,34]. However, the possibility remains that the intracellular processing of the opioid sig nal requires the presence of androgens.…”

Section: Discussionmentioning

confidence: 85%

Chronic Morphine Treatment Induces Hypersensitivity to Testosterone-Negative Feedback in Castrated Male Rats

Gabriel¹,

Simpkins²,

Kalra

et al. 1985

Neuroendocrinology

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Studies were undertaken to determine the effects of chronic stimulation of opiate receptors on the negative feedback effects of testosterone (T) on luteinizing hormone (LH) secretion in the male rat. In an initial study, castrated male rats received replacement levels of T (2 ng/ml) or chronic morphine (M) treatment for 7 days. When initiated at the time of castration, both T and M treatments prevented the castration-induced hypersecretion of LH. However, when the treatments commenced 2 weeks after castration, only T restored LH secretion to the low levels seen in intact rats. In a second study, rats castrated 2 weeks previously were exposed to chronic M or placebo (control) treatment in the presence of various dosages of T. In rats receiving T alone, LH secretion was unaffected at T levels up to 600 pg/ml serum, but thereafter there was a dose-dependent suppression of LH release by T. Serum T levels which reduced LH secretion by 50 % were estimated to be 966 pg/ml. In contrast, in castrated rats receiving both M and T treatment, a 50% reduction in LH secretion was estimated to be at 300 pg T/ml serum and maximal inhibition of LH secretion was achieved at serum T levels of greater than 600 pg/ml. Neither T alone nor M plus T treatment altered the responsiveness of the anterior pituitary to LHRH in vitro. These findings indicate that M may enhance the sensitivity of the hypothalamus to T feedback by approximately 3-fold and raise the possibility of the existence of an opioid-sensitive neural component which may modulate the negative feedback effects of T on LH secretion.

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Section: Discussionmentioning

confidence: 85%

Chronic Morphine Treatment Induces Hypersensitivity to Testosterone-Negative Feedback in Castrated Male Rats

Gabriel¹,

Simpkins²,

Kalra

et al. 1985

Neuroendocrinology

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“…The precise anatomical and biochemical characteriza tion of the interactions between opioid-and steroid-contai ning neuronal systems has not been clearly elucidated, but the initial observations of Hahn and Fishman [11] appeared to provide very strong biochemical evidence of such a rela tionship in the adult male rat. Thus, it is not surprising that this widely quoted paper has stimulated a great deal of re search effort.Unfortunately, no independent group [4,5,7,29,30] has been able to replicate the results of Hahn and Fishman [II] since the initial publication of their results in 1979, generat ing a great deal of controversy in this potentially important area of research. In response to this growing body of nega tive data, Hahn and Fishman [12] recently reexamined this entire issue and concluded that procedural differences can fully explain the discrepancies in the literature.…”

mentioning

confidence: 86%

“…In the present studies, we have attempted to incorporate the critical procedural variables recently identified by Hahn and Fishman [12] to independently replicate their re sults since earlier extensive studies in our laboratories failed to reproduce their findings [4], However, in our ear lier work we employed a filtration method identified by these investigators as inappropriate and our method of membrane preparation was also different. Thus, we felt it was obligatory to reexamine this question in an effort to definitively resolve this long-standing controversy in the lit erature regarding the potentially important possibility that the regulation of opioid receptors is steroid-dependent in the male rat.…”

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confidence: 96%

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Reevaluation of the Effects of Castration on Naloxone-Sensitive Opiate Receptors in the Male Rat Brain

Cicero¹,

O’Connor²,

Bell³

1987

Neuroendocrinology

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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).

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“…However, the literature on the effects exerted by castration on brain opioid receptors is scanty and controversial. Hahn & Fishman (1979, 1985 have found that the binding of naltrexone, naloxone and diprenorphine to opioid receptors in the rat whole brain is increased by orchidectomy, but Wilkinson, Herdon & Wilson (1981), Diez & Roberts (1982) and Cicero, Newman & Meyer (1983) have found that neither castration nor subsequent androgen replacement therapy modify the binding capacity of the whole brain and of the hypothalamus for a number of opioid ligands. An alternative possibility is that castration might have modified the bioavailability of other brain neurotransmitters involved in the control of prolactin secretion (Müller, Nisticò & Scapagnini, 1977).…”

Section: Resultsmentioning

confidence: 99%