Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Localization of prolactin receptor in the newt brain

  • 177 Accesses

  • 14 Citations


In the male newt Cynops pyrrhogaster, prolactin (PRL) acts directly on the central nervous system and induces courtship behavior. As a step to elucidate the localization of neurons on which PRL acts, we developed a polyclonal antibody against an oligopeptide having a sequence completely identical with a part of the sequence of PRL receptors (PRLRs) of two species of newts, C. pyrrhogaster and C. ensicauda, and performed an immunohistochemical study with this antibody. PRLR-immunoreactive cells were observed in the medial amygdala, anterior preoptic area, magnocellular preoptic nucleus, suprachiasmatic nucleus, nucleus of the periventricular organ, ventral hypothalamic nucleus, and choroid plexus. We also performed in situ hybridization with a 35S-labeled newt PRLR antisense RNA probe and detected signals in the preoptic area and choroid plexus. Colocalization of both PRLR-like immunoreactivity and arginine vasotocin-like or mesotocin-like immunoreactivity was demonstrated in the magnocellular preoptic nucleus. This is the first report of PRLR localization in the amphibian brain.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathway and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268

  2. Bridges RS, Numan M, Ronsheim PM, Mann PE, Lupini CE (1990) Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats. Proc Natl Acad Sci USA 87:8003–8007

  3. Buntin JD, Ruzycki E (1987) Characteristics of prolactin binding sites in the brain of the ring dove (Streptopelia risoria). Gen Comp Endocrinol 65:243–253

  4. Chadwick CS (1941) Identity of prolactin with water drive factor in Triturus viridescens. Proc Soc Exp Biol Med 45:335–337

  5. Chiu S, Wise PM (1994) Prolactin receptor mRNA localization in the hypothalamus by in situ hybridization. J Neuroendocrinol 6:191–199

  6. De Vito WJ (1988) Distribution of immunoreactive prolactin in the male and female rat brain: effects of hypophysectomy and intraventricular administration of colchicines. Neuroendocrinology 47:284–289

  7. Dent LN (1975) Integumentary effects of prolactin in the lower vertebrates. Am Zool 15:923–935

  8. Emanuele NV, Jurgens JK, Halloran MM, Tentler JJ, Lawrence AM, Kelley MR (1992) The rat prolactin gene is expressed in brain tissue: detection of normal and alternative spliced prolactin messenger RNA. Mol Endocrinol 6:35–42

  9. Fuxe K, Hokfelt T, Eneroth P, Gustafsson JA, Skett P (1977) Prolactin-like immunoreactivity: localization in nerve terminals of rat hypothalamus. Science 196:899–900

  10. Goudie RB, Horne CHW, Wilkinson PC (1966) A simple method for producing antibody specific to a single selected diffusible antigen. Lancet II:1224–1226

  11. Grattan DR, Pi XJ, Andrews ZB, Augustine RA, Kokay IC, Summerfield MR, Todd B, Bunn SJ (2001) Prolactin receptors in the brain during pregnancy and lactation: implications for behavior. Horm Behav 40:115–124

  12. Kawamoto K, Kawashima S (1985) Changes of vasopressin- and oxytocin-immunoreactive neurons after hypophysectomy in young and old mice. Exp Geront 20:295–304

  13. Kikuyama S, Nakano R, Yasumasu I (1975) Synergistic action of prolactin and androgen on the cloacal glands of the newt. Comp Biochem Physiol A 51:823–826

  14. Kikuyama S, Yamamoto K, Seki T (1980) Prolactin and its role in growth, metamorphosis and reproduction in amphibians. Gunma Symp Endocrinol 17:3–13

  15. Kikuyama S, Seshimo H, Shirama K, Kato T, Noumura T (1986) Interaction of prolactin with sex steroid in oviduct and tail of newts, Cynops pyrrhogaster. Zool Sci 3:131–138

  16. Kikuyama S, Toyoda F, Ohmiya Y, Matsuda K, Tanaka S, Hayashi H (1995) Sodefrin: a female-attracting peptide pheromone in newt cloacal glands. Science 267:1643–1645

  17. Kikuyama S, Tanaka S, Moore FL (2003) Endocrinology of reproduction. In: Sever DM (ed) Reproductive biology and phylogeny of ulodela. Science Publishers, New Hampshire, pp 275–321

  18. Malacarne G, Giacoma C (1980) Effects of lesions to the rostral preoptic area on courtship behaviour in the male crested newt Triturus cristatus carnifex (Laur). Monit Zool Ital (NS) 14:9–17

  19. Malacarne G, Giacoma C, Vellano C, Mazzi V (1982) Prolactin and sexual behavior in the crested newt (Triturus cristatus carnifex Laur). Gen Comp Endocrinol 47:139–147

  20. Matsuda K, Yamamoto K, Kikuyama S (1990a) Purification and properties of newt prolactin. Gen Comp Endocrinol 77:63–69

  21. Matsuda K, Yamamoto K, Kikuyama S (1990b) Development and application of homologous radioimmunoassay for newt prolactin. Gen Comp Endocrinol 79:83–88

  22. Matsukawa H, Hasunuma I, Katoh T, Yamamoto K, Miura S, Fujita T, Kikuyama S (2004) Expression of prolactin receptor mRNA in the abdominal gland of the newt Cynops ensicauda. Comp Biochem Physiol B 138:79–88

  23. Matsumoto A, Arai Y, Kouki T, Kikuyama S (1995) Comparison of Mauthner cell size in sexually developed and undeveloped male red-bellied newts. J Neurobiol 28:126–132

  24. Matsumoto A, Toyoda F, Kouki T, Kikuyama S (1997) Hormonal alteration of synaptic input to Mauthner cells of the adult male red-bellied newts. Zool Sci 14:651–657

  25. Mazzi V, Vellano C, Toscano C (1967) Anigonadal effects of prolactin in adult male crested newt (Triturus cristatus carnifex Laur). Gen Comp Endocrinol 8:320–324

  26. Mejia S, Torner LM, Jeziorski MC, Gonzalez C, Morales MA, Escalera GM, Clapp C (2003) Prolactin and 16K prolactin stimulate release of vasopressin by a direct effect on hypothalamo-neurohypophyseal system. Endocrine 20:155–161

  27. Moore FL, Zoeller RT (1979) Endocrine control of amphibian sexual behavior: evidence for a neurohormone-androgen interaction. Horm Behav 13:207–213

  28. Mosconi G, Yamamoto K, Kikuyama S, Carnevali O, Mancuso A, Vellano C (1994) Seasonal changes of plasma prolactin concentration in the reproduction of the crested newt (Triturus carnifex Laur). Gen Comp Endocrinol 95:342–349

  29. Muccioli G, Guardabassi A, Pattono P (1990) Biochemical study of prolactin binding sites in Xenopus laevis brain and choroid plexus. J Exp Zool 253:311–318

  30. Nevalainen, MT, Valve EM, Ingleton PM, Harkonen PL (1996) Expression and hormone regulation of prolactin receptor in rat dorsal and lateral prostate. Endocrinology 137:3078–3088

  31. Oliver C, Mical RS, Porter JC (1977) Hypothalamic-pituitary vasculature: evidence for retrograde blood flow in the pituitary stalk. Endocrinology 101:598–604

  32. Parker SL, Armstrong WE, Sladek CD, Grosvenor CE, Crowley WR (1991) Prolactin stimulates the release of oxytocin in lactating rats: evidence for a physiological role via an action at the neural lobe. Neuroendocrinology 53:503–510

  33. Polzonetti-Magni AM, Carnevali O, Yamamoto K, Kikuyama S (1995) Growth hormone and prolactin in amphibian reproduction. Zool Sci 12:683–694

  34. Porter JC, Barnea A, Cramer OM, Parker CR Jr (1978) Hypothalamic peptide and catecholamine secretion: roles for portal and retrograde blood flow in the pituitary stalk in the release of hypothalamic dopamine and pituitary prolactin and LH. Clin Obstet Gynaecol 5:271–282

  35. Roky R, Paut-Pagano L, Goffin V, Kitahama K, Valatx JL, Kelly PA, Jouvet M (1996) Distribution of prolactin receptors in the rat forebrain. Neuroendocrinology 63:422–429

  36. Santos CRA, Ingleton PM, Cavaco JEB, Kelly PA, Edery M, Power DM (2001) Cloning, characterization, and tissue distribution of prolactin receptor in the sea bream (Sparus aurata). Gen Comp Endocrinol 121:32–47

  37. Sarker DK (1988) Immunoneutralization of oxytocin attenuates preovulatory prolactin secretion during proestrus in the rat. Neuroendocrinology 48:214–216

  38. Schuler LA, Nagel RJ, Gao J, Horseman ND, Kessler MA (1997) Prolactin receptor heterogeneity in bovine fetal and maternal tissues. Endocrinology 138:3187–3194

  39. Toyoda F, Ito M, Tanaka S, Kikuyama S (1993) Hormonal induction of male courtship behavior in the Japanese newt, Cynops pyrrhogaster. Horm Behav 27:511–522

  40. Toyoda F, Matsuda K, Yamamoto K, Kikuyama S (1996) Involvement of endogenous prolactin in the expression of courtship behavior in the newt, Cynops pyrrhogaster. Gen Comp Endocrinol 102:191–196

  41. Toyoda F, Yamamoto K, Ito Y, Tanaka S, Yamashita M, Kikuyama S (2003) Involvement of arginine vasotocin in reproductive events in the male newt, Cynops pyrrhogaster. Horm Behav 44:346–353

  42. Toyoda F, Hasunuma I, Yamamoto K, Yamashita M, Kikuyama S (2005) Prolactin acts centrally to enhance newt courtship behavior. Gen Comp Endocrinol 141:172–177

  43. Walsh RG, Slaby FJ, Posner BI (1987) A receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid. Endocrinology 120:1846–1850

  44. Yamamoto K, Toyoda F, Tanaka F, Hayashi H, Kikuyama S (1996) Radioimmunoassay of a newt sex pheromone, sodefrin, and the influence of hormones on its level in the abdominal gland. Gen Comp Endocrinol 104:356–363

  45. Yamamoto T, Nakayama Y, Matsuda Y, Abe S-I (1998) Cloning and expression of a cDNA encoding a prolactin receptor of the Japanese red-bellied newt, Cynops pyrrhogaster. Zool Sci 15:741–747

  46. Yamamoto K, Kawai Y, Hayashi T, Ohe Y, Hayashi H, Toyoda F, Kawahara G, Iwata T, Kikuyama S (2000) Silefrin, a sodefrin-like pheromone in the abdominal gland of the sword tailed newt, Cynops ensicauda. FEBS Lett 472:267–270

  47. Yazawa T, Yamamoto K, Kikuyama S, Abe S-I (1999) Elevation of plasma prolactin concentrations by low temperature is the cause of spermatogonial cell death in the newt, Cynops pyrrhogaster. Gen Comp Endocrinol 113:302–311

Download references

Author information

Correspondence to Sakae Kikuyama.

Additional information

This study was supported by a research grant from Waseda University to S.K. and by a grant-in-aid from the Ministry of Education, Science, and Culture of Japan to I.H., F.T., and S.K.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hasunuma, I., Toyoda, F., Yamamoto, K. et al. Localization of prolactin receptor in the newt brain. Cell Tissue Res 320, 477–485 (2005). https://doi.org/10.1007/s00441-004-1041-0

Download citation


  • Prolactin receptor
  • Arginine vasotocin
  • Mesotocin
  • Brain
  • Newts, Cynops pyrrhogaster
  • C. ensicauda (Urodela)