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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Nipples


High impact information on Nipples

  • Whereas relaxin is required for development of the mammary nipples in rats and mice, it is essential for prepartum development of glandular parenchyma in pregnant pigs [6].
  • Reinstatement was not achieved by coating the washed nipples with the saliva of virgin females eating the same diet, the parturient mother's urine, isotonic saline, amyl acetate, or vanilla extract [7].
  • Each agent was dissolved in DMSO, and one-sixth of the total dose was injected under each of six nipples on the right side [8].
  • Fluoxetine-induced anaesthesia of vagina and nipples [9].
  • N-Nitrosodibenzylamine (NDBzA) is a contaminant found frequently in rubber baby bottle nipples and pacifiers [10].

Chemical compound and disease context of Nipples

  • Perinatal administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual differentiation in rats induces female-like anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, suprainguinal ectopic scrota/testes, a vaginal pouch, epididymal granulomas, and small to absent sex accessory glands in male offspring [11].
  • A case of hyperkeratosis of the nipples in a patient with adenocarcinoma of the prostate treated with diethylstilbestrol is described herein [12].

Biological context of Nipples

  • The nipples of rlx-/- animals do not enlarge significantly during pregnancy, and their histology retains the appearance of the virgin state [13].
  • We recently demonstrated that relaxin-dependent development of the mammary nipples during the second half of pregnancy is required for pup survival during lactation in the rat [14].
  • An almost fully feminized phenotype of 10-12 nipples was observed in animals that had malformations in T-dependent tissues, whereas 6 or more nipples were observed in animals with malformation in DHT-dependent tissues [15].
  • These findings indicate that the burst amplitude mainly depends on the amount of afferent suckling signals arising from the nipples on the side opposite to the recording side, and that there may exist bilateral summation centres coordinating with the synchronization mechanism of milk-ejection bursts of oxytocin neurones [16].
  • Hypertrophic nipples were seen in 42% of surviving female fetuses prenatally exposed to 2.0 mg/kg of ethinyl estradiol singly on day 11 of gestation [17].

Anatomical context of Nipples


Associations of Nipples with chemical compounds

  • We conclude that relaxin stimulates the growth of rat mammary nipples at least in part through direct actions in the nipples, and that estrogen is not required for these actions [18].
  • Tissue cross-sections (6 microns) obtained from the midpoint of mammary nipples were stained with either Gomori's trichrome stain (to visualize collagen) or orcein (to visualize elastin) [14].
  • As adults, flutamide-exposed males had nipples [21].
  • These data also suggest that although linuron-mediated retention of areolae on PND 13 and nipples at necropsy may be suggestive of altered testosterone-mediated reproductive development seen in adult rats, these endpoints are not predictive [22].
  • Only DDE-treated animals retained nipples on PND 13 [23].

Gene context of Nipples

  • Mutant females deficient for the Lgr7 receptor have grossly undeveloped nipples and are unable to feed their progeny [24].
  • We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples [25].
  • The total amount of immunoreactive CGRP was significantly higher in the nipples from the pregnant and the lactating rats when compared to SP [26].
  • Plasma PRL levels were low in rats separated from their litters, but they increased when pups were returned to the cage, attached to the nipples of the mother, and suckled [27].
  • Mothers which had previously suckled 12 pups (Group 1) showed a graded increase in the amount of oxytocin released during a 3 h suckling test when the number of pups applied to the nipples was increased from six to eight or ten [28].

Analytical, diagnostic and therapeutic context of Nipples


  1. A partial long arm deletion of chromosome 7:46,XY,del(7)(q32). Kousseff, B.G., Hsu, L.Y., Paciuc, S., Hirschhorn, K. J. Med. Genet. (1977) [Pubmed]
  2. Early manifestations of the carbohydrate-deficient glycoprotein syndrome. Petersen, M.B., Brostrøm, K., Stibler, H., Skovby, F. J. Pediatr. (1993) [Pubmed]
  3. Autosomal recessive ectodermal dysplasia, cleft lip/palate, mental retardation, and syndactyly: the Zlotogora-Ogur syndrome. Rodini, E.S., Richieri-Costa, A. Am. J. Med. Genet. (1990) [Pubmed]
  4. Congenital disorder of glycosylation type Ia: a clinicopathological report of a newborn infant with cerebellar pathology. Aronica, E., van Kempen, A.A., van der Heide, M., Poll-The, B.T., van Slooten, H.J., Troost, D., Rozemuller-Kwakkel, J.M. Acta Neuropathol. (2005) [Pubmed]
  5. Partial deletion of distal 17q. Bridge, J., Sanger, W., Mosher, G., Buehler, B., Nelson, R., Welsh, M., Newland, J., Kafka, M. Am. J. Med. Genet. (1985) [Pubmed]
  6. Relaxin's physiological roles and other diverse actions. Sherwood, O.D. Endocr. Rev. (2004) [Pubmed]
  7. First suckling response of the newborn albino rat: the roles of olfaction and amniotic fluid. Teicher, M.H., Blass, E.M. Science (1977) [Pubmed]
  8. Lack of tumorigenicity of cholesterol epoxides and estrone-3,4-quinone in the rat mammary gland. el-Bayoumy, K., Ji, B.Y., Upadhyaya, P., Chae, Y.H., Kurtzke, C., Rivenson, A., Reddy, B.S., Amin, S., Hecht, S.S. Cancer Res. (1996) [Pubmed]
  9. Fluoxetine-induced anaesthesia of vagina and nipples. Michael, A., Mayer, C. The British journal of psychiatry : the journal of mental science. (2000) [Pubmed]
  10. Analysis of tissue-specific lacZ mutations induced by N-nitrosodibenzylamine in transgenic mice. Jiao, J., Douglas, G.R., Gingerich, J.D., Soper, L.M. Carcinogenesis (1997) [Pubmed]
  11. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Gray, L.E., Ostby, J., Monosson, E., Kelce, W.R. Toxicology and industrial health. (1999) [Pubmed]
  12. Estrogen-induced hyperkeratosis of the nipple. Mold, D.E., Jegasothy, B.V. Cutis; cutaneous medicine for the practitioner. (1980) [Pubmed]
  13. Mice without a functional relaxin gene are unable to deliver milk to their pups. Zhao, L., Roche, P.J., Gunnersen, J.M., Hammond, V.E., Tregear, G.W., Wintour, E.M., Beck, F. Endocrinology (1999) [Pubmed]
  14. Monoclonal antibodies specific for rat relaxin. VII. Passive immunization with monoclonal antibodies throughout the second half of pregnancy prevents development of normal mammary nipple morphology and function in rats. Kuenzi, M.J., Sherwood, O.D. Endocrinology (1992) [Pubmed]
  15. Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues. McIntyre, B.S., Barlow, N.J., Foster, P.M. Toxicol. Sci. (2001) [Pubmed]
  16. Milk ejection bursts of supraoptic oxytocin neurones during bilateral and unilateral suckling in the rat. Wang, Y.F., Negoro, H., Honda, K. J. Neuroendocrinol. (1996) [Pubmed]
  17. Effect of ethinyl estradiol on development of mouse fetuses. Yasuda, Y., Kihara, T., Nishimura, H. Teratology (1981) [Pubmed]
  18. Relaxin acts directly on rat mammary nipples to stimulate their growth. Kuenzi, M.J., Connolly, B.A., Sherwood, O.D. Endocrinology (1995) [Pubmed]
  19. Identification of specific relaxin-binding cells in the human female. Kohsaka, T., Min, G., Lukas, G., Trupin, S., Campbell, E.T., Sherwood, O.D. Biol. Reprod. (1998) [Pubmed]
  20. Identification of specific relaxin-binding cells in the cervix, mammary glands, nipples, small intestine, and skin of pregnant pigs. Min, G., Sherwood, O.D. Biol. Reprod. (1996) [Pubmed]
  21. Nipple development and pup-induced prolactin release in male rats treated prenatally with the antiandrogen flutamide. Tate-Ostroff, B.A., Bridges, R.S. Psychoneuroendocrinology (1988) [Pubmed]
  22. Male rats exposed to linuron in utero exhibit permanent changes in anogenital distance, nipple retention, and epididymal malformations that result in subsequent testicular atrophy. McIntyre, B.S., Barlow, N.J., Foster, P.M. Toxicol. Sci. (2002) [Pubmed]
  23. Interactive effects of TCDD and p,p'-DDE on male reproductive tract development in in utero and lactationally exposed rats. Loeffler, I.K., Peterson, R.E. Toxicol. Appl. Pharmacol. (1999) [Pubmed]
  24. Genetic targeting of relaxin and insl3 signaling in mice. Feng, S., Bogatcheva, N.V., Kamat, A.A., Agoulnik, A.I. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  25. Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. Lundquist, K., Kohler, S., Rouse, R.V. Am. J. Surg. Pathol. (1999) [Pubmed]
  26. Calcitonin gene-related peptide (CGRP) in the nipple of the rat mammary gland. Thulesen, J., Rasmussen, T.N., Schmidt, P., Holst, J.J., Poulsen, S.S. Histochemistry (1994) [Pubmed]
  27. Relationship of prolactin release in lactating rats to milk ejection, sleep state, and ultrasonic vocalization by the pups. Voloschin, L.M., Tramezzani, J.H. Endocrinology (1984) [Pubmed]
  28. Relationship between the suckling-induced release of oxytocin and prolactin in the urethane-anaesthetized lactating rat. Wakerley, J.B., O'Neill, D.S., ter Haar, M.B. J. Endocrinol. (1978) [Pubmed]
  29. Substance P immunoreactivity in the rat mammary nipple and the effects of capsaicin treatment on lactation. Traurig, H., Papka, R.E., Saria, A., Lembeck, F. Naunyn Schmiedebergs Arch. Pharmacol. (1984) [Pubmed]
  30. Making vaccines more acceptable--methods to prevent and minimize pain and other common adverse events associated with vaccines. Jacobson, R.M., Swan, A., Adegbenro, A., Ludington, S.L., Wollan, P.C., Poland, G.A. Vaccine (2001) [Pubmed]
  31. Long-term predictable nipple projection following reconstruction. Few, J.W., Marcus, J.R., Casas, L.A., Aitken, M.E., Redding, J. Plast. Reconstr. Surg. (1999) [Pubmed]
  32. Case report: a man with breast dysphoria. Kremer, J., den Daas, H.P. Archives of sexual behavior. (1990) [Pubmed]
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