Sex Differences in Brain and Plasma β-Endorphin Content following Testosterone, Dihydrotestosterone and Estradiol Administration to Gonadectomized Rats
Abstract
Aims: The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E 2 V) on brain and plasma β-endorphin (β-END) concentrations in gonadectomized rats of both sexes. Methods: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 μg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 μg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E 2 V was administered subcutaneously at 0.05 mg/kg/day. β-END levels were measured in different brain areas and plasma. Results: Ovariectomy (OVX) induced a significant decrease in β-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E 2 V significantly increased β-END concentration in all brain areas and in plasma. In the OCX group, T and E 2 V did not influence β-END concentrations in different hypothalamic areas. However, they produced a significant rise in β-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect β-END levels at any dose administered, either in males or females. Conclusions: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement.
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Testosterone administration increased β-endorphin levels in the brains and plasma of ovariectomized rats.
“Pluchino et al70 showed that testosterone administration increased β-endorphin levels in the brains and plasma of ovariectomized rats.”
From Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone (2023) · cites this paper as [70]
Cites
Endocrinology of the stress response
Charmandari, E., Tsigos, C., & Chrousos, G. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.67.040403.120816 · Cited by 1,799 · see citing works
Effects of testosterone on sexual function in men: results of a meta‐analysis
Isidori, A. M., Giannetta, E., Gianfrilli, D., Greco, E. A., Bonifacio, V., Aversa, A., Isidori, A., Fabbri, A., & Lenzi, A. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02350.x · Cited by 492 · cited 1× · see citing works
“There is evidence to suggest that aging men might benefit from exogenous supplementation of T in terms of overall sexual satisfaction, well-being and cognitive senescence [4, 5] .”
The endocrinology of sexual arousal
Bancroft, J. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06233 · Cited by 398 · cited 1× · see citing works
“In addition, the administration of exogenous opiates can induce an intense feeling of pleasure, which has been linked to or-gasm, followed by a state of relaxation and calm [12] .”
Smith, Y. R., Stohler, C. S., Nichols, T. E., Bueller, J. A., Koeppe, R. A., & Zubieta, J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5223-05.2006 · Cited by 377 · see citing works
Gender and Age Influences on Human Brain Mu-Opioid Receptor Binding Measured by PET
Zubieta, J., Dannals, R. F., & Frost, J. J. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.6.842 · Cited by 335 · see citing works
Androgen therapy in women: An Endocrine Society clinical practice guideline
Wierman, M. E., Basson, R., Davis, S. R., Khosla, S., Miller, K. K., Rosner, W., & Santoro, N. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1121 · Cited by 301 · cited 1× · see citing works
“…deficiency syndrome in pre-and postmenopausal women, Pluchino/Ninni/Casarosa/Giannini/ Merlini/Cubeddu/Luisi/Cela/Genazzani Neuroendocrinology 2009;89:411–423 412 enhancing sexual desire and pleasure, as well as decreasing mood instability and preventing an altered sense of well-being [1] .”
Investigation, treatment and monitoring of late-onset hypogonadism in males
Nieschlag, E., Swerdloff, R. S., Hm, B., Gooren, L. J., Kaufman, J., Legros, J.-J., Lunenfeld, B., Morley, J., Schulman, C., Wang, C., et al. (2005) · The Aging Male · doi:10.1080/13685530500130969 · Cited by 242 · see citing works
Estrogen, cognition and female ageing
Genazzani, A. R., Pluchino, N., Luisi, S., & Luisi, M. (2007) · Human Reproduction Update · doi:10.1093/humupd/dml042 · Cited by 237 · see citing works
Self-citationNeuropeptides and sexual behaviour
Argiolas, A. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00068-8 · Cited by 148 · see citing works
Ribeiro, S. C. M., Kennedy, S. E., Smith, Y. R., Stohler, C. S., & Zubieta, J. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.08.011 · Cited by 147 · see citing works
Przewłocki, R., & Przewłocka, B. (2005) · Current Pharmaceutical Design · doi:10.2174/1381612054865055 · Cited by 143 · see citing works
Roselli, C. E., Salisbury, R. L., & Resko, J. A. (1987) · Endocrinology · doi:10.1210/endo-121-6-2205 · Cited by 116 · see citing works
Roselli, C. E., & Klosterman, S. A. (1998) · Endocrinology · doi:10.1210/endo.139.7.6101 · Cited by 110 · see citing works
Petraglia, F., Peñalva, A., Locatelli, V., Cocchi, D., Panerai, A. E., Genazzani, A. R., & Müller, E. E. (1982) · Endocrinology · doi:10.1210/endo-111-4-1224 · Cited by 104 · see citing works
Self-citationEndogenous opiates and behavior: 2005
Bodnar, R. J., & Klein, G. E. (2006) · Peptides · doi:10.1016/j.peptides.2006.07.011 · Cited by 85 · see citing works
Chowen, J. A., Fraser, H. M., Vician, L. J., DAMASSA, D. A., Clifton, D. K., & Steiner, R. A. (1989) · Endocrinology · doi:10.1210/endo-124-4-1697 · Cited by 79 · see citing works
Chowen, J. A., Argente, J., Vician, L. J., Clifton, D. K., & Steiner, R. A. (2008) · Neuroendocrinology · doi:10.1159/000125647 · Cited by 74 · see citing works
Endocrinology of Menopausal Transition and Its Brain Implications
Genazzani, A. R., Bernardi, F., Pluchino, N., Begliuomini, S., Lenzi, E., Casarosa, E., & Luisi, M. (2005) · CNS Spectrums · doi:10.1017/s1092852900023142 · Cited by 70 · see citing works
Self-citationChowen, J. A., Clifton, D. K., & Steiner, R. A. (1989) · Endocrinology · doi:10.1210/endo-124-6-2875 · Cited by 65 · see citing works
Genazzani, A. R., Petraglia, F., Facchinetti, F., Grasso, A., Alessandrini, G., & Volpe, A. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000293687 · Cited by 57 · see citing works
Self-citationKeja, J. A., Stoof, J. C., & Kits, K. S. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019134 · Cited by 51 · see citing works
Testosterone and Cognition in Normal Aging and Alzheimers Disease: An Update
Driscoll, I. F., & Resnick, S. M. (2007) · Current Alzheimer Research · doi:10.2174/156720507779939878 · Cited by 48 · see citing works
Steroid regulation of brain aromatase expression in glia: Female preoptic and vocal motor nuclei
Forlano, P. M., & Bass, A. H. (2005) · Journal of Neurobiology · doi:10.1002/neu.20178 · Cited by 47 · see citing works
Testosterone and men's quality of life
Moncada, I. (2006) · The Aging Male · doi:10.1080/13685530601003180 · Cited by 45 · see citing works
The release of β-endorphin and the neuropeptide-receptor mismatch in the brain
MacMillan, S. J. A., Mark, M. A., & Duggan, A. W. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00223-6 · Cited by 44 · see citing works
Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women
Stomati, M., Bersi, C., Rubino, S., Palumbo, M. A., Comitini, G., Genazzani, A. D., Santre, M., Petraglia, F., & Genazzani, A. R. (1997) · Maturitas · doi:10.1016/s0378-5122(97)00073-x · Cited by 44 · see citing works
Self-citationGenazzani, A. R., Stomati, M., Bernardi, F., Luisi, S. V., Casarosa, E., Puccetti, S., Genazzani, A. D., Palumbo, M. A., & Luisi, M. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.08.022 · Cited by 39 · see citing works
Self-citationAre POMC neurons targets for sex steroids in the arcuate nucleus of the rat?
Fodor, M., & de Waal, H. A. D. (2001) · Neuroreport · doi:10.1097/00001756-200112210-00027 · Cited by 29 · see citing works
Carter, D., Williams, T. D. M., & Lightman, S. L. (1986) · Journal of Endocrinology · doi:10.1677/joe.0.1110239 · Cited by 27 · see citing works
Krzanowska, E. K., & Bodnar, R. J. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00110-2 · Cited by 27 · see citing works
Sex differences in androgen-regulated cytochrome P450 aromatase mRNA in the rat brain
Roselli, C. E., Abdelgadir, S. E., Jorgensen, E., & Resko, J. A. (1996) · Endocrine · doi:10.1007/bf02738657 · Cited by 24 · see citing works
Saland, L. C., Carr, J. A., Samora, A., & Tejeda, D. (1992) · Peptides · doi:10.1016/0196-9781(92)90049-9 · Cited by 13 · see citing works
Gender effect on the right–left discrimination task in a sample of heroin-dependent patients
Liu, N., Li, B., Wilson, F. A. W., Ma, Y., & Hu, X. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0031-6 · Cited by 12 · see citing works
Naloxone and Its Analeptic Effect
Gillman, M. A., & LICHTIGFELD, F. J. (1983) · Anesthesiology · doi:10.1097/00000542-198303000-00020 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis
Becker, J. B., Perry, A. N., & Westenbroek, C. (2012) · Biology of Sex Differences · doi:10.1186/2042-6410-3-14 · Cited by 315 · see citing works
Sex hormone activity in alcohol addiction: Integrating organizational and activational effects
Lenz, B., Müller, C. P., Stoessel, C., Sperling, W., Biermann, T., Hillemacher, T., Bleich, S., & Kornhuber, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.001 · Cited by 136 · see citing works
Sex differences in pain and opioid mediated antinociception: Modulatory role of gonadal hormones.
Nasser, S. A., & Afify, E. A. (2019) · Life Science · doi:10.1016/j.lfs.2019.116926 · Cited by 83 · see citing works
Endogenous opiates and behavior: 2009
Bodnar, R. J. (2010) · Peptides · doi:10.1016/j.peptides.2010.09.016 · Cited by 61 · see citing works
Sex Differences in Opioid-Mediated Effects: Role of Androgens
Sharp, J. L., Pearson, T., & Smith, M. A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104522 · Cited by 60 · see citing works
Impact of sex on pain and opioid analgesia: a review
Fullerton, E. F., Doyle, H. H., & Murphy, A. Z. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.08.001 · Cited by 55 · see citing works
Jiang, C. S., Dileone, R., Pittenger, C., & Duman, R. S. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02796-0 · Cited by 42 · see citing works
Rojas, P. S., Rosemarie Fritsch, M., Rojas, R., Jara, P., & Fiedler, J. L. (2011) · Psychiatry Research · doi:10.1016/j.psychres.2011.04.032 · Cited by 37 · see citing works
Kranz, G. S., Zhang, B. B. B., Handschuh, P. A., Ritter, V., & Lanzenberger, R. R. (2020) · Cortex · doi:10.1016/j.cortex.2020.04.005 · Cited by 36 · see citing works
Fanton, L. E., de Macedo, C. G., Torres-Chávez, K. E., Fischer, L., & Tambeli, C. H. (2016) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2016.07.005 · Cited by 31 · see citing works
Neurosteroid influences on sensitivity to ethanol
Helms, C. M., Rossi, D. J., & Grant, K. A. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00010 · Cited by 30 · see citing works
Why We Still Need To Speak About Sex Differences and Sex Hormones in Pain
Aloisi, A. M. (2017) · Pain and Therapy · doi:10.1007/s40122-017-0084-3 · Cited by 25 · see citing works
Estrogen mediation of hormone responses to exercise
Kraemer, R. R., Francois, M., & Castracane, V. D. (2012) · Metabolism · doi:10.1016/j.metabol.2012.03.009 · Cited by 21 · see citing works
Association of V89L SRD5A2 polymorphism with craving and serum leptin levels in male alcohol addicts
Lenz, B., Schöpp, E., Müller, C. P., Bleich, S., Hillemacher, T., & Kornhuber, J. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2770-5 · Cited by 20 · see citing works
Effect of estetrol on Beta-Endorphin level in female rats
Pluchino, N., Drakopoulos, P., Casarosa, E., Freschi, L., Petignat, P., Yaron, M., & Genazzani, A. R. (2015) · Steroids · doi:10.1016/j.steroids.2015.01.003 · Cited by 18 · see citing works
Self-citationCrespi, B. J., & Evans, S. F. (2023) · Journal of Pain Research · doi:10.2147/jpr.s389166 · Cited by 17 · see citing works
Anabolic–androgenic steroid effects on nociception and morphine antinociception in male rats
Tsutsui, K., Wood, R. I., & Craft, R. M. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.04.023 · Cited by 16 · see citing works
Sex differences in neonatal outcomes following prenatal opioid exposure
Madurai, N. K., Jantzie, L. L., & Yen, E. (2024) · Frontiers in Pediatrics · doi:10.3389/fped.2024.1357970 · Cited by 11 · see citing works
Bontempi, L., & Bonci, A. (2020) · Science Signaling · doi:10.1126/scisignal.aba1169 · Cited by 10 · see citing works
Wen, J., Wang, J., Tang, X., Deng, S., Dai, J., Li, X., & Cai, W. (2019) · PubMed Central · Cited by 6 · see citing works
Testosterone modulation of ethanol effects on the �‑opioid receptor kinetics in castrated rats
Khalil, R., & Humann, J. (2019) · Biomedical Reports · doi:10.3892/br.2019.1230 · Cited by 3 · see citing works
β-Endorphin influences sedative and ataxic effects of alcohol
Stea, S. G., & Grisel, J. E. (2023) · Alcohol · doi:10.1016/j.alcohol.2023.09.004 · Cited by 3 · see citing works
Hayvanlarda Beta-endorfinin Üreme Sistemi ile İlişkisi
Akalın, P. P., Başpınar, N., Bucak, M. N., & Çoyan, K. (2011) · Erciyes Üniversitesi Veteriner Fakültesi Dergisi · Cited by 1 · see citing works
Dimorphism of Human Brain: The Basis of the Gender Differences
Genazzani, A. R., Giannini, A., & Simoncini, T. (2017) · ISGE series · doi:10.1007/978-3-319-41433-1_1 · Cited by 1 · see citing works
Self-citationEffects of ⧍-5 and ⧍-4 Androgens on the Brain
Pluchino, N., zani, A. R. G., & Gynaecologist (2008) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2008.04.02.110
Self-citationMadurai, N. K., Williams, I. A. R., Craig, A. M., Guyer, L., Clemens, K. J., & Jantzie, L. L. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-26576-1.00015-0
- Authors
- Pluchino, N., Ninni, F., Casarosa, E., Giannini, A., Merlini, S., Cubeddu, A., Luisi, M., Cela, V., & Genazzani, A. R.
- Affiliations
- University of Pisa (IT)
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 89
- Issue
- 4
- Pages
- 411-423
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2085146257
- Cited by
- 27
- References
- 34
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2012: 4
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-03-19)
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- beta-endorphin, sex differences, testosterone, dihydrotestosterone, estradiol valerate, gonadectomy, ovariectomy, orchiectomy, hypothalamus, anterior pituitary, neurointermediate lobe, opioid system, rats
- MeSH terms
- Animals, beta-Endorphin, Brain, Estradiol, Female, Male, Orchiectomy, Ovariectomy, Sex Characteristics, Dihydrotestosterone, Testosterone, Rats, Wistar, Rats
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