Endocrinology, Vol 124, 1160-1172, Copyright © 1989 by Endocrine Society

ARTICLES

Sigma-receptors in endocrine organs: identification, characterization, and autoradiographic localization in rat pituitary, adrenal, testis, and ovary

SA Wolfe Jr, SG Culp and EB De Souza
Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland 21224.

We have used a variety of selective radioligands to identify and localize sigma- and phencyclidine (PCP)-binding sites in rat endocrine organs. [3H]Haloperidol-labeled sigma-receptors were identified in membrane homogenates of rat pituitary, adrenal, testis, and ovary which had kinetic and pharmacological characteristics similar to those of the well characterized sigma-receptors in rat cerebellum. The highest density of sigma-receptors was present in the ovary, with progressively lower densities present in the testis, pituitary, adrenal, and cerebellum, respectively. In autoradiographic studies, sigma-receptors [labeled with d-3-(3-hydroxyphenyl)N-(1-propyl-2,3-[3H]piperidine or [3H]1,3-di-(2-tolyl)guanidine] were discretely localized within the endocrine tissues. In the pituitary, the highest density of sigma- receptors was found in the anterior lobe. In the adrenal, sigma- receptors were localized primarily in the cortex. In the testis, sigma- receptors were present in highest concentrations in the ductuli efferentes and ductus epididymis; lower densities of binding sites were present in the seminiferous tubules, and no binding was seen in the interstitial tissue. In the ovary, sigma-receptors were localized in high density in the maturing follicles, and lower densities were present in resting follicles. After hypophysectomy, there were relative increases in the densities of sigma receptors in the remaining tissue in the adrenal gland and testis. In contrast, hypophysectomy resulted in a marked depletion of sigma-binding sites in the ovary. The data from hypophysectomized rats indicate that the highest densities of sigma-receptors in the ovary are localized to (LH-dependent) maturing follicles, while sigma-binding sites in adrenal and testis are localized to cells that are not dependent on trophic maintenance by the pituitary. In contrast, high affinity PCP receptors were not detected in pituitary, adrenal, testis, or ovary either by homogenate binding studies with 3,4-[3H]N-[1-(2-thienyl)cyclohexyl]piperidine or in vitro autoradiography using 3,4-[3H]N-[1-(2-thienyl)cyclohexyl]piperidine and d-[3H]5-methyl-10,11-dihydro-5H-dibenzo-[a,d] + cyclohepten-5,10-imine. In summary, the data suggest that the reported endocrine effects of PCP and the prototypic sigma-receptor agonist N-allylnormetazocine are probably mediated either through direct action on sigma-receptors in the pituitary and/or target endocrine organs or by actions on sigma- and/or PCP receptors in brain.

This article has been cited by other articles:

				D. J. Rowland, Z. Tu, J. Xu, D. Ponde, R. H. Mach, and M. J. Welch Synthesis and In Vivo Evaluation of 2 High-Affinity 76Br-Labeled {sigma}2-Receptor Ligands J. Nucl. Med., June 1, 2006; 47(6): 1041 - 1048. [Abstract] [Full Text] [PDF]

				A. Mukherjee, T. K. Prasad, N. M. Rao, and R. Banerjee Haloperidol-associated Stealth Liposomes: A POTENT CARRIER FOR DELIVERING GENES TO HUMAN BREAST CANCER CELLS J. Biol. Chem., April 22, 2005; 280(16): 15619 - 15627. [Abstract] [Full Text] [PDF]

				M. Manikkam, Y. Li, B. M. Mitchell, D. E. Mason, and L. C. Freeman Potassium Channel Antagonists Influence Porcine Granulosa Cell Proliferation, Differentiation, and Apoptosis Biol Reprod, July 1, 2002; 67(1): 88 - 98. [Abstract] [Full Text] [PDF]

				J. W. Proksch, W. B. Gentry, and S. M. Owens The Effect of Rate of Drug Administration on the Extent and Time Course of Phencyclidine Distribution in Rat Brain, Testis, and Serum Drug Metab. Dispos., July 1, 2000; 28(7): 742 - 747. [Abstract] [Full Text]

				M. Schaefer, U. F. Habenicht, M. Bräutigam, and T. Gudermann Steroidal Sigma Receptor Ligands Affect Signaling Pathways in Human Spermatozoa Biol Reprod, July 1, 2000; 63(1): 57 - 63. [Abstract] [Full Text]

				C. S. John, B. J. Vilner, B. C. Geyer, T. Moody, and W. D. Bowen Targeting Sigma Receptor-binding Benzamides as in Vivo Diagnostic and Therapeutic Agents for Human Prostate Tumors Cancer Res., September 1, 1999; 59(18): 4578 - 4583. [Abstract] [Full Text] [PDF]

				O. Jbilo, H. Vidal, R. Paul, N. De Nys, M. Bensaid, S. Silve, P. Carayon, D. Davi, S. Galiegue, B. Bourrie, et al. Purification and Characterization of the Human SR 31747A-binding Protein. A NUCLEAR MEMBRANE PROTEIN RELATED TO YEAST STEROL ISOMERASE J. Biol. Chem., October 24, 1997; 272(43): 27107 - 27115. [Abstract] [Full Text] [PDF]