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The complexities of receptor binding
Editorial Commentary Readers on this topic need to be familiar with the guidelines setup by the European Academy of Andrology and the Europe Molecular Genetics Quality Network. Paul G. McDonough, M.D., Associate Editor Medical College of Georgia Augusta, Georgia
nutritional status regarding selenium and 2) evaluation of thyroid function. Roy Moncayo, M.D.a,b Helga Moncayo, M.D.b a Clinical Department of Nuclear Medicine Medical University of Innsbruck b WOMED, Innsbruck, Austria April 27, 2008
doi:10.1016/j.fertnstert.2008.05.022 REFERENCES The complexities of receptor binding To the Editor: We read with great interest the article by Moses-Kolko et al. (1) on the topic of reduced serotonin 1A binding potential in postpartum depression. In their discussion they propose that their findings may be related to other components of the postpartum endocrine milieu. We would like to present data that expand on this proposal. In a recent study by Negro et al. (2) an association was found between diminished levels of selenium and thyroid dysfunction in the postpartum period. Their sequential evaluation showed clearly that selenium losses can occur during pregnancy and that postpartum alterations could be corrected by selenium supplementation. In nonpregnant patients we have also found an association between low levels of selenium and cases of thyroid disease, especially subacute or silent thyroiditis (3). The study by Moses-Kolko et al. (1) did not present any data on thyroid function. In addition to the immediate relation of selenium to thyroid function, one should not forget the relevance of selenium in brain function in relation to monoamines and oxidative processes (4). The brain depends on sufficient selenium supply to maintain the adequacy of selenoprotein P. From the standpoint of nuclear medicine, it is important to revise our models related to receptor imaging. Current data strongly suggest that the dynamic processes related to receptor binding should not be viewed on a one-to-one relation (i.e., one tracer and one ligand). New biochemical data show that G-protein coupled receptors can present a complex ligand structure (i.e., receptor mosaics), including homodimers and heterodimers. The serotonin receptor system is a complex building whose diversity depends on genomic interactions (5). In view of these characteristics, the message from Moses-Kolko et al. (1) as to ‘‘. receptor reductions .’’ has to be taken with caution. We agree with the authors’ conclusion: ‘‘Recognition of this neurobiological deficit in postpartum depression may be useful in the development of treatments and prevention strategies for this disabling disorder’’ (1). We propose that research on treatment options for postpartum depression should consider two essential points: 1) evaluation of the Fertility and Sterility
1. Moses-Kolko EL, Wisner KL, Price JC, Berga SL, Drevets WC, Hanusa BH, et al. Serotonin 1A receptor reductions in postpartum depression: a positron emission tomography study. Fertil Steril 2008;89: 685–92. 2. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 2007;92:1263–8. 3. Moncayo R, Kroiss A, Oberwinkler M, Karakolcu F, Starzinger M, Kapelari K, et al. The role of selenium, vitamin C, and zinc in benign thyroid diseases and of Se in malignant thyroid diseases: low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma. BMC Endocrine Disorders 2008;8:2. 4. Casta~no A, Cano J, Machado A. Low selenium diet affects monoamine turnover differentially in substantia nigra and striatum. J Neurochem 1993;61:1302–7. 5. Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P. Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res 2006;326:553–72.
doi:10.1016/j.fertnstert.2008.06.024 Reply of the Authors: We thank Drs. Roy and Helga Moncayo for their interest in our manuscript (1). We are grateful for the opportunity to explore the relationship between perinatal depression, hypothalamic-pituitary-thyroid (HPT) function, and 5-serotonin (HT) 1A receptor binding. Subjects underwent HPT function screening with a battery of T4, TSH, thyroglobulin, and thyroid peroxidase antibody concentrations. Only subjects who were euthyroid were included (T4 between 5 and 12 mg/dL; TSH between 0.3 and 5 mIU/mL). All subjects lacked thyroid antibodies with the exception of one perinatally depressed subject with equivocally positive concentrations of thyroglobulin antibodies (92 IU/mL) and thyroid peroxidase antibodies (93 IU/mL). The T4 (mean SD) did not differ between perinatally depressed (7.56 1.80) and healthy controls (7.06 0.72). The TSH showed a nonsignificant trend (P ¼ .055) toward being increased in perinatally depressed (1.8 0.78) relative to healthy controls (1.22 0.28). Because TSH trended toward differing between groups, we explored the correlation between TSH concentrations and 5-HT 1A receptor binding, as assessed with [11C]WAY100635- positron emission tomography imaging, 465
nutritional status regarding selenium and 2) evaluation of thyroid function. Roy Moncayo, M.D.a,b Helga Moncayo, M.D.b a Clinical Department of Nuclear Medicine Medical University of Innsbruck b WOMED, Innsbruck, Austria April 27, 2008
doi:10.1016/j.fertnstert.2008.05.022 REFERENCES The complexities of receptor binding To the Editor: We read with great interest the article by Moses-Kolko et al. (1) on the topic of reduced serotonin 1A binding potential in postpartum depression. In their discussion they propose that their findings may be related to other components of the postpartum endocrine milieu. We would like to present data that expand on this proposal. In a recent study by Negro et al. (2) an association was found between diminished levels of selenium and thyroid dysfunction in the postpartum period. Their sequential evaluation showed clearly that selenium losses can occur during pregnancy and that postpartum alterations could be corrected by selenium supplementation. In nonpregnant patients we have also found an association between low levels of selenium and cases of thyroid disease, especially subacute or silent thyroiditis (3). The study by Moses-Kolko et al. (1) did not present any data on thyroid function. In addition to the immediate relation of selenium to thyroid function, one should not forget the relevance of selenium in brain function in relation to monoamines and oxidative processes (4). The brain depends on sufficient selenium supply to maintain the adequacy of selenoprotein P. From the standpoint of nuclear medicine, it is important to revise our models related to receptor imaging. Current data strongly suggest that the dynamic processes related to receptor binding should not be viewed on a one-to-one relation (i.e., one tracer and one ligand). New biochemical data show that G-protein coupled receptors can present a complex ligand structure (i.e., receptor mosaics), including homodimers and heterodimers. The serotonin receptor system is a complex building whose diversity depends on genomic interactions (5). In view of these characteristics, the message from Moses-Kolko et al. (1) as to ‘‘. receptor reductions .’’ has to be taken with caution. We agree with the authors’ conclusion: ‘‘Recognition of this neurobiological deficit in postpartum depression may be useful in the development of treatments and prevention strategies for this disabling disorder’’ (1). We propose that research on treatment options for postpartum depression should consider two essential points: 1) evaluation of the Fertility and Sterility
1. Moses-Kolko EL, Wisner KL, Price JC, Berga SL, Drevets WC, Hanusa BH, et al. Serotonin 1A receptor reductions in postpartum depression: a positron emission tomography study. Fertil Steril 2008;89: 685–92. 2. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 2007;92:1263–8. 3. Moncayo R, Kroiss A, Oberwinkler M, Karakolcu F, Starzinger M, Kapelari K, et al. The role of selenium, vitamin C, and zinc in benign thyroid diseases and of Se in malignant thyroid diseases: low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma. BMC Endocrine Disorders 2008;8:2. 4. Casta~no A, Cano J, Machado A. Low selenium diet affects monoamine turnover differentially in substantia nigra and striatum. J Neurochem 1993;61:1302–7. 5. Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P. Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res 2006;326:553–72.
doi:10.1016/j.fertnstert.2008.06.024 Reply of the Authors: We thank Drs. Roy and Helga Moncayo for their interest in our manuscript (1). We are grateful for the opportunity to explore the relationship between perinatal depression, hypothalamic-pituitary-thyroid (HPT) function, and 5-serotonin (HT) 1A receptor binding. Subjects underwent HPT function screening with a battery of T4, TSH, thyroglobulin, and thyroid peroxidase antibody concentrations. Only subjects who were euthyroid were included (T4 between 5 and 12 mg/dL; TSH between 0.3 and 5 mIU/mL). All subjects lacked thyroid antibodies with the exception of one perinatally depressed subject with equivocally positive concentrations of thyroglobulin antibodies (92 IU/mL) and thyroid peroxidase antibodies (93 IU/mL). The T4 (mean SD) did not differ between perinatally depressed (7.56 1.80) and healthy controls (7.06 0.72). The TSH showed a nonsignificant trend (P ¼ .055) toward being increased in perinatally depressed (1.8 0.78) relative to healthy controls (1.22 0.28). Because TSH trended toward differing between groups, we explored the correlation between TSH concentrations and 5-HT 1A receptor binding, as assessed with [11C]WAY100635- positron emission tomography imaging, 465