T

FIGURE 4-23 Amino acid sequence and proposed membrane topography of the human ocytocin receptor. Reproduced with permission from Kimura, T., Azuma, C., Takemura, M., Inoue, T., Kikuchi, T., Kubota, Y., Ogita, K., Saji, F., and Tanizawa, O. (1993). Regul. Pept. 45, 73-77.

hormones travel down the pituitary stalk. Consequently, damage by trauma or tumors will also impede the output of VP and OT. Water balance will be affected, and frequency of urination will be controlled medically by the administration of a hormone or hormone analog to treat diabetes insipidus. Presumably males will have less consequences from OT deficiency. This disease is somewhat rare in occurrence. In principle, a number of conditions can lead to the failure of VP expression from the posterior pituitary or of its effectiveness at the site of action. Damage by tumors or cysts, encephalitis, granulomatous diseases such as tuberculosis, sarcoidosis, syphilis, and meningitis, and arteriosclerosis to the secretory apparatus or the hypo-thalamohypophyseal portal system may occur. Vascular destruction may also occur to the portal system as a result of degenerative diseases. Brain tumors may be a most important factor. A major cause is trauma. Hereditary diseases may also play a role with abnormal functions at the level of the hypothalamus-pituitary or the kidney. The latter case is presumed to alter the expression or function of VP receptors. Other unsubstantiated possibilities are increased degradation of VP or development of autoimmune antibodies.

OT induces uterine contractions at the start of labor since greatly increased numbers of OT receptors near labor have been induced in the myometrium; however, OT in physiological doses does not induce labor during pregnancy. Hypophysectomized females can have a normal labor, indicating either that the important amounts of OT originate from the fetus or that other factors besides OT are involved. It is still not known whether OT initiates labor. Prior to labor, it has been suggested that relaxin may cause the release of opioids that inhibit the secretion of OT until the time of parturition. These have been discussed in this chapter and in Chapter 14. Excess or deficiency of OT has, so far, not been associated with a disease process.

Oxytocin

Asn-Cys-Pro-Leu-Gly-NH2

"Asn-Cys-Pro-Leu-Gly • NH2 Octapeptide

NADP+

GSSG Reductase

Glu SH NAsn-Cys-Pro-Leu-Gly-NH2

Dihydrooxytocin

Cystine aminopeptidase

Further degradation (Lysosomes—Amino acids (?) )

FIGURE 4-24 Degradation of posterior pituitary hormones. OT transhydrogenase (human placenta) is similar to degrading enzymes of other tissues and is also similar to enzymes degrading insulin. These enzymes presumably also degrade VP.

References

A. Books

DeGroot, L. J. (1995). "Endocrinology", 3rd ed. Vol 1. Iyengar, R. and Birnbaumer, L., eds. (1990). "G Proteins." Academic Press, San Diego.

B. Review Articles

Argiolas, A., and Gessa, G. L. (1991). Central functions of oxytocin. Neurosci. Biobehav. Rev. 15, 217-231.

Falke, N. (1991). Modulation of oxytocin and vasopressin release at the level of the neurohypophysis. Prog. Neurobiol. 36, 465-484.

Jenkins, J. S., and Nussey, S. S. (1991). The role of oxytocin: present concepts. Clin. Endocrinol. 34, 515-525.

Knepper, M. A. (1994). The aquaporin family of molecular water channels. Proc. Natl. Acad. Sei. USA 91, 6255-6258.

Mohr, E., and Richter, D. (1994). Vasopressin in the regulation of body functions. /. Hypertension 12, 345-348. Mohr, E., Myerhof, W., and Richter, D. (1992). The hypothalamic hormone oxytocin: from gene expression to signal transduction. Rev. Physiol. Biochem. Pharmacol. 121, 31-48. Mohr, E., Meyerhof, W., and Richter, D. (1995). Vasopressin and oxytocin: Molecular biology and evolution of the peptide hormones and their receptors. Vitamins Hormones 51, 235-266. Vallotton, M. B. (1991). The multiple faces of vasopressin receptors. Mol. Cell. Endocrinol. 78, C73-C76.

C. Research Papers

Breslow, E. (1993). Structure and folding properties of neurophysin and its peptide complexes: biological implications. Regul. Pept. 45, 15-19.

Chen, L., Rose, J. P., Breslow, E„ Yang, D., Chang, W.-R., Furey, W. F., Sax, M., and Wang, B.-C. (1991). Crystal structure of a bo vine neurophysin II dipeptide complex at 2.8 A determined from the single-wavelength anomalous scattering signal of an incorporated iodine atom. Proc. Natl. Acad. Sci. USA 88,4240-4244.

Dyer, R. G. (1988). Oxytocin and parturition—new complications. /. Endocrinol. 116, 167-168.

Kimura, T., Azuma, C., Takemura, M., Inoue, T., Kikichi, T., Kubota, Y., Ogita, K., Saji, F., and Tanizawa, O. (1993). Molecular cloning of a human oxytocin receptor. Regul. Pept. 45, 73-77.

Miller, F. D., Chibbar, R., and Mitchell, B. F. (1993). Synthesis of oxytocin in amnion, chorion and decidua: a potential paracrine role for oxytocin in the onset of human parturition. Regul. Pept. 45, 247-251.

Perraudin, V., Delarue, C., Lefebvre, H., Contesse, V., Kuhn, J.-M., and Vaudry, H. (1993). Vasopressin stimulates Cortisol secretion from human adrenocortical tissue through activation of Vj receptors. /. Clin. Endocrinol. Metab. 76, 1522-1528.

Thibonnier, M., Bayer, A. L., and Leng, Z. (1993). Cytoplasmic and nuclear signaling pathways of Vrvascular vasopressin receptors. Regul. Pept. 45, 79-84.

Wood, S. P., Tickle, I. J., Treharne, A. M., Pitts, J. E., Mascarenhas, Y., Li, J. Y„ Husain, J., Cooper, S., Blundell, T. M., Hruby, V. J., Buku, A., Fischman, A. J., and Wyssbrod, H. R. (1986). Crystal structure analysis of deaminooxytocin: conformational flexibility and receptor binding. Science 232, 633-636.

Yasin, S., Costa, A., Trainer, P., Windle, R., Forsling, M. L., and Grossman, A. (1993). Nitric oxide modulates the release of vasopressin from rat hypothalamic explants. Endocrinology 133,14661469.

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