1. Chapter 5 The Hypothalamus—Pituitary System in Non-Mammalian Vertebrates Copyright © 2013 Elsevier Inc. All rights reserved.

2. Figure 5-1 Hatschek’s pit in the cephalochordate amphioxus. (A) Cross-section through the oral cavity (OC) of an adult animal showing two basic chordate features: dorsal nerve cord (NE) and notochord (NO). Hatschek’s pit (H) appears on the dorsal pharyngeal surface similar to the location of Rathke’s pouch in vertebrate embryos. (B) Enlargement of Hatschek’s pit showing immunoreactive metenkephalin-like material (arrows). (Reprinted with permission from Nozaki, M. and Gorbman, A., Zoological Science, 9, 387–395, 1992.) 2 Copyright © 2013 Elsevier Inc. All rights reserved.

3. Figure 5-2 The neural complex of a tunicate. (From Kawamura, K., Kouki, T., Kawahara, G., Kikuyama, S. 2002. Hypophyseal development in vertebrates from amphibians to mammals. General and Comparative Endocrinology 126, 130–135.) 3 Copyright © 2013 Elsevier Inc. All rights reserved.

4. Figure 5-3 Generalized hypothalamo–hypophysial axis in fishes. Note the lack of a Pars tuberalis in fishes. Abbreviations, ME, median eminence; OC, optic chiasm; PI, pars intermedia; PN, pars nervosa; POA, preoptic area. 4 Copyright © 2013 Elsevier Inc. All rights reserved.

5. Figure 5-4 Regions of the teleost adenohypophysis. The terminologies of Green (1951) and Pickford and Atz (1957) are compared for the three histologically distinct regions (1, 2, and 3). The saccus vasculosis (SV) is not part of the pituitary but is a prominent nearby structure. Only the Green nomenclature is used in the text. 5 Copyright © 2013 Elsevier Inc. All rights reserved.

6. Figure 5-5 Comparative anatomy of the fish pituitary. The neurohypophysis is indicated by the darker color and the pars intermedia is shown in black. Approximate distributions of cell types secreting tropic hormones are indicated by letters. A, corticotropin; G, gonadotropins; M, melanotropin; P, prolactin; P+, somatolactin; S, growth hormone or somatotropin; T, thyrotropin, ?, unidentified. (Adapted with permission from Schreibman, M. P. (1986). Pituitary Gland. In “Vertebrate Endocrinology: Fundamentals and Biomedical Implications. Volume 1, Morphological Considerations” (P.K.T. Pang and M.P. Schreibman, eds), pp 11–56. Academic Press, Orlando, Florida.) 6 Copyright © 2013 Elsevier Inc. All rights reserved.

7. Figure 5-6 Neuroendocrine systems of Atlantic hagfish (Myxine glutinosa). Colored cells in adenohypophysis represent gonadotropes. Abbreviations: AH, adenohypophysis; CT, connective tissue; HN, hypothalamic nucleus; NH, neurohypophysis; POC, postoptic commissure; PON, preoptic nucleus; III, third ventricle. (Adapted with permission from Sower, S.A. and Kawauchi, H., in “Hormones and eproduction of Vertebrates. Vol. 1. Fishes” (D.O. Norris and K.H. Lopez, Eds.), Academic Press, San Diego, CA, 2011, pp. 193– 208.) 7 Copyright © 2013 Elsevier Inc. All rights reserved.

8. Figure 5-7 Neuroendocrine systems of sea lamprey (Petromyzon marinus). Abbreviations: NH, neurohypophysis; PI, pars intermedia; PON, preoptic nucleus; PPD, proximal pars distalis; RPD, rostral pars distalis. See Appendix A for other abbreviations. (Adapted with permission from Kawauchi, H. and Sower, S.A., General and Comparative Endocrinology, 148, 3–19, 2006. Sower, S.A. and Kawauchi, H., Reproduction in agnathan fishes: lampreys and hagfishes. In “Hormones and Reproduction of Vertebrates. Vol. 1. Fishes” (D.O. Norris and K.H. Lopez, Eds.), Academic Press, San Diego, CA, 2011, pp. 193–208.) 8 Copyright © 2013 Elsevier Inc. All rights reserved.

9. Figure 5-8 The saccus vasculosus of rainbow trout (Oncorhynchus mykiss). (A) Note the closeness of the saccus vasculosus (SV) and adenohypophysis (PPD, PI). (B) Higher magnification of SV. Arrows indicate coronet cells. Note accumulation of secretory material along the SV lumina. rbcs, red blood cells. 9 Copyright © 2013 Elsevier Inc. All rights reserved.

10. Figure 5-9 Prolactin (PRL), corticotropin (ACTH), and growth hormone (GH) in the teleost pituitary. Immunoreactive demonstration of (A,B) lactotropes, (C,D) corticotropes, and (E,F) somatotropes in the pituitary of Alosa spidissima. Asterisks indicate cavities. Abbreviations: HYP, hypothalamus; NH, neurohypophysis, PI, pars intermedia, PPD, proximal pars distalis; RPD, rostral pars distalis. (Reprinted with permission from Laiz- Carrion, R. et al., General and Comparative Endocrinology, 132, 454–464, 2003.) 10 Copyright © 2013 Elsevier Inc. All rights reserved.

11. Figure 5-10 Somatolactin (SL) cells in teleost pars intermedia. Immunoreactive SL cells in the pars intermedia (P) of the neurointermediate lobe of the teleost Alosa sapidissima demonstrated with use of an antibody to salmon SL (anti-aSL). See Figure 5-9 for an explanation of abbreviations. (Reprinted with permission from Laiz-Carrion, R. et al., General and Comparative Endocrinology, 132, 454–464, 2003.) 11 Copyright © 2013 Elsevier Inc. All rights reserved.

12. Figure 5-11 Comparative anatomy of the tetrapod pituitary. See Figure 5-4 for an explanation of symbols. (Adapted with permission from Schreibman, M.P., in “Vertebrate Endocrinology: Fundamentals and Biomedical Implications. Vol. 1. Morphological Considerations” (P.K.T. Pang and M. Schreibman, Eds.), Academic Press, Orlando, FL, 1986, pp. 11–56.) 12 Copyright © 2013 Elsevier Inc. All rights reserved.

13. Figure 5-12 Amphibian pars tuberalis. Transmission electron micrograph of granular cells in the pars tuberalis of the frog, Rana pipiens. Two cell types can be identified on the basis of granule size. (Photograph courtesy of Dr. Kevin T. Fitzgerald.) 13 Copyright © 2013 Elsevier Inc. All rights reserved.

14. Figure 5-13 Cytology of the amphibian pars distalis. Dark-appearing cells are stained with antibodies selective for different pituitary hormones. (A) Immunoreactive prolactin-secreting cells. (B) Immunoreactive growth hormone-secreting cells. (C) Immunoreactive FSH-secreting cells. (D) Immunoreactive LH-secreting cells. (E) Immunoreactive corticotropin-secreting cells. (F) Immunoreactive thyrotropin-secreting cells. (A–D) Japanese newt (Cynops pyrrhogaster); (E) adult bullfrog (Rana catesbeiana); (F) postmetamorphic toad (Bufo calamita). (Parts A to D are courtesy of Shigeyasu Tanaka and Sakae Kikuyama, Waseda University, Tokyo. Part E is reprinted with permission from Tanaka, S. et al., General and Comparative Endocrinology, 77, 88–97, 1990. Part F is reprinted with permission from Garcia-Navarro, S. et al., General and Comparative Endocrinology, 71, 116–123, 1988.) 14 Copyright © 2013 Elsevier Inc. All rights reserved.

15. Figure 5-14 Hypothalamus of sea lamprey (Petromyzon marinus). (A) Sagittal section. (B,C) Cross-sections at levels indicated in Part A. See text or Appendix A for an explanation of abbreviations. (Adapted with permission from Matsumoto, A. and Ishii, S., “Atlas of Endocrine Organs: Vertebrates and Invertebrates,” Springer-Verlag, Berlin, 1989.) 15 Copyright © 2013 Elsevier Inc. All rights reserved.

16. Figure 5-15 Hypothalamus of a representative teleost, the Atlantic eel (Anguilla anguilla). (A) Sagittal section. (B,C) Cross-sections at levels indicated in Part A. APERIV, anterior periventricular nucleus; ATN, anterior tuberal nucleus; ON, optic nerve; OT, optic tract; POPERIV, periventricular preoptic nucleus; PTN, posterior tuberal nucleus. See text or Appendix A for other abbreviations. (Adapted with permission from Matsumoto, A. and Ishii, S., “Atlas of Endocrine Organs: Vertebrates and Invertebrates,” Springer-Verlag, Berlin, 1989.) 16 Copyright © 2013 Elsevier Inc. All rights reserved.

17. Figure 5-16 Hypothalmaus of an amphibian, the American bullfrog (Rana catesbeiana). (A) Sagittal section. (B,C) Cross-sections at levels indicated in Part A. PVO, paraventricular organ. See text or Appendix A for other abbreviations. (Adapted with permission from Matsumoto, A. and Ishii, S., “Atlas of Endocrine Organs: Vertebrates and Invertebrates,” Springer-Verlag, Berlin, 1989.) 17 Copyright © 2013 Elsevier Inc. All rights reserved.

18. Figure 5-17 Hypothalamus of a reptile, the Japanese forest ratsnake (Elaphe conspicillata). (A) Sagittal section. (B,C,D) Cross-sections at levels indicated in Part A. AHA, DHA, LHA, PHA = anterior, dorsal, lateral, posterior hypothalamic area, respectively; PVO, paraventrocular organ. See text or Appendix A for other abbreviations. (Adapted with permission from Matsumoto, A. and Ishii, S., “Atlas of Endocrine Organs: Vertebrates and Invertebrates,” Springer-Verlag, Berlin, 1989.) 18 Copyright © 2013 Elsevier Inc. All rights reserved.

19. Figure 5-18 Hypothalamus of a bird, the Japanese quail (Coturnix coturnix japonicus). (A) Sagittal section. (B,C,D) Cross-sections at levels indicated in Part A. TSM, septomesencephalic tract. See Figure 5-17 or Appendix A for other abbreviations. (Adapted with permission from Matsumoto, A. and Ishii, S., “Atlas of Endocrine Organs: Vertebrates and Invertebrates,” Springer-Verlag, Berlin, 1989.) 19 Copyright © 2013 Elsevier Inc. All rights reserved.

20. Figure 5-19 A comparison of human FSH and GPB5 with GPB5 from amphioxus, a protochordate. (Reprinted with permission from Tando, Y. and Kubokawa, K., General and Comparative Endocrinology, 162, 328–339, 2009.) 20 Copyright © 2013 Elsevier Inc. All rights reserved.

21. Figure 5-20 Phylogeny of  -subunit genes for the glycoprotein tropic hormones. Note that the genes for each tropic hormone form a distinct cluster for all species examined. Although not shown, FSH  and LH  genes from a reptile (Reeves’s turtle) cluster near the respective bird gonadotropin. (Based on studies by Oba, Y. et al., Comparative Biochemistry and Physiology B, 129, 441–448, 2001; Querat, B. et al., Biology of Reproduction, 70, 356–363, 2004.) 21 Copyright © 2013 Elsevier Inc. All rights reserved.

22. Figure 5-21 GpH Receptor evolution within vertebrates. (A) Follicle-stimulating hormone receptor (FSHR). (B) Luteinizing hormone receptor (LHR). (C) Thyrotropin receptor (TSHR). Note that the teleosts can be separated into two groups indicating gene differences coding for somewhat different receptors. (Adapted with permission from Levavi-Sivan, B. et al., General and Comparative Endocrinology, 165, 412–437, 2010.) 22 Copyright © 2013 Elsevier Inc. All rights reserved.

23. Figure 5-21 cont’d. GpH Receptor evolution within vertebrates. (A) Follicle-stimulating hormone receptor (FSHR). (B) Luteinizing hormone receptor (LHR). (C) Thyrotropin receptor (TSHR). Note that the teleosts can be separated into two groups indicating gene differences coding for somewhat different receptors. (Adapted with permission from Levavi-Sivan, B. et al., General and Comparative Endocrinology, 165, 412–437, 2010.) 23 Copyright © 2013 Elsevier Inc. All rights reserved.

24. Figure 5-21 cont’d. GpH Receptor evolution within vertebrates. (A) Follicle-stimulating hormone receptor (FSHR). (B) Luteinizing hormone receptor (LHR). (C) Thyrotropin receptor (TSHR). Note that the teleosts can be separated into two groups indicating gene differences coding for somewhat different receptors. (Adapted with permission from Levavi-Sivan, B. et al., General and Comparative Endocrinology, 165, 412–437, 2010.) 24 Copyright © 2013 Elsevier Inc. All rights reserved.

25. Figure 5-22 Phylogeny of growth hormone (GH) genes. Note that primate GH is distinctly different from other mammals. (Adapted with permission from Daza, D.O. et al., Annals of the New York Academy of Sciences, 1163, 491–493, 2009.) 25 Copyright © 2013 Elsevier Inc. All rights reserved.

26. Figure 5-23 Phylogeny of Prolactin (PRL) genes. Two forms of PRL (PRLa,PRLb) are present in all teleosts tested as a result of an additional gene duplication in teleosts. (Adapted with permission from Daza, D.O. et al., Annals of the New York Academy of Sciences, 1163, 491–493, 2009.) 26 Copyright © 2013 Elsevier Inc. All rights reserved.

27. Figure 5-24 Phylogeny of somatolactin (SL) genes within fishes. Note that two distinct forms (  and  ) are found in some species, including zebrafish and rainbow trout (not shown here). Note that the African lungfish SL is very much like teleost SL. (Adapted with permission from Daza, D.O. et al., Annals of the New York Academy of Sciences, 1163, 491–493, 2009.) 27 Copyright © 2013 Elsevier Inc. All rights reserved.

28. Figure 5-25 Phylogeny receptor genes for prolactin (A), growth hormone (GH), and somatolactin (SL) receptors. Note the anomalous position of the GHR for the Japanese eel (Anguilla japonica) that is clustered with SLRs. (Adapted with permission from Daza, D.O. et al., Annals of the New York Academy of Sciences, 1163, 491–493, 2009.) 28 Copyright © 2013 Elsevier Inc. All rights reserved.

29. Figure 5-26 Comparison of teleost prolactin (PRL) and growth hormone (GH) to mammalian forms. Note that tilapia PRL is like mouse GH with respect to the disulfide bonds, whereas sturgeon GH structure is more like mouse PRL. 29 Copyright © 2013 Elsevier Inc. All rights reserved.

30. Figure 5-27 Phylogeny of Growth Hormone (GH) and Prolactin (PRL) in Amphibia. (A) GH. (B) PRL. Some fishes (teleosts and holosteans) are included for comparison. (Adapted with permission from Yang, L. et al., General and Comparative Endocrinology, 165, 177–180, 2010.) 30 Copyright © 2013 Elsevier Inc. All rights reserved.

31. Figure 5-28 Hormonal content within POMC. (A) Modifications that take place in a corticotrope. (B) Modifications that take place in a melanotrope. (Adapted with permission from Dores, R.M. and Baron, A.J., Annals of the New York Academy of Sciences, 1220, 34–48, 2011.) 31 Copyright © 2013 Elsevier Inc. All rights reserved.

32. Figure 5-29 Binding domains of the a-MSH/ACTH peptide for melanocortin receptors. The motif HFRW binds to MC1R, MC3R, MC4R, and MC5R whereas the KKRRP motif is believed to bind to the MC2R. PPS is the posttranslational processing site removed when ACTH is cleaved in melanotropes. Removal of PSS results in lost of binding ability to MC2R by the products (  -MSH or CLIP). (Adapted with permission from Dores, R.M. and Baron, A.J., Annals of the New York Academy of Sciences, 1220, 34–48, 2011.) 32 Copyright © 2013 Elsevier Inc. All rights reserved.

33. Figure 5-30 Evolution of POMC. The appearance of two separate POMC-like molecules in corticotropes (POC) and melanotropes (POM) of lampreys may indicate a derived condition that appeared in the modern lampreys after their separation from the ancestral vertebrate condition (as suggested within the dashed box). (Adapted with permission from Dores, R.M. and Baron, A.J., Annals of the New York Academy of Sciences, 1220, 34–48, 2011.) 33 Copyright © 2013 Elsevier Inc. All rights reserved.

34. Figure 5-31 Production of melanosomes. Premelanosomes differentiate from Golgi vesicles. They exhibit tyrosinase activity and synthesize melanin by polymerizing tyrosine. Once melanization of these organelles is complete, they are called melanosomes. 34 Copyright © 2013 Elsevier Inc. All rights reserved.

35. Figure 5-32 Melanophores and melanocytes. This terminology is based on the Sixth International Pigment Cell Conference held in 1966. Melanophores can disperse their melanosomes uniformly in the cytoplasm or concentrate them to varying degrees around the nucleus. 35 Copyright © 2013 Elsevier Inc. All rights reserved.

36. Figure 5-33 Immunoreactive ACTH in lamprey pituitary gland. (A) Dark brown staining for immunoreactivity to sea lamprey ACTH in the rostral pars distalis (RPD) of Mordacia. (B) Immunoreactive MSH in the pars intermedia (PI). (Reprinted with permission from Takahashi, A. et al., General and Comparative Endocrinology, 148, 72–78, 2006.) 36 Copyright © 2013 Elsevier Inc. All rights reserved.

37. Figure 5-34 Phylogeny of Chordate GnRH genes. 1R and 3R represent genome duplications that occurred during evolution of vertebrates. 2R is a proposed additional partial or complete genome duplication. (Adapted with permission from Sower, S.A. et al., General and Comparative Endocrinology, 161, 20–29, 2009.) 37 Copyright © 2013 Elsevier Inc. All rights reserved.

38. Figure 5-35 Distribution patterns for different types of GnRHs in teleost brains. (Adapted with permission from Kah, O. and Dufour, S., in “Hormones and Reproduction of Vertebrates. Vol 1. Fishes” (D.O. Norris and K.H. Lopez, Eds.), Academic Press, San Diego, CA, 2011, pp. 15–42.) 38 Copyright © 2013 Elsevier Inc. All rights reserved.

39. Figure 5-36 GnRH-R gene evolution. Note the inclusion of tunicate and amphioxus receptors in this phylogeny. *Indicates new data provided by this source. (Adapted with permission from Roch, G.J. et al., General and Comparative Endocrinology, 171, 1e16, 2011.) 39 Copyright © 2013 Elsevier Inc. All rights reserved.

40. Figure 5-37 Phylogeny of kiss1 & kiss2 based on cDNAs. Adapted with permission from Zohar, Y., Muoz- Cueto, J.A., Elizur, A., Kah, O. (2010). Neuroendocrinology of reproduction in teleost fish. Gen. Comp. Endocrinol. 165, 438-455. 40 Copyright © 2013 Elsevier Inc. All rights reserved.

41. Figure 5-38 Kisspeptin (kiss1 or kiss2) and dopamine (DA) regulation of gonadotropin secretion in teleosts. Inhibitory DA neurons innervate both GnRH neurons and luteinizing hormone-secreting gonadotropes (LH cell). Kiss1 or kiss2 neurons stimulate GnRH release and possibly have direct effects on LH release operating through GPR54 (kiss1r) receptors. Gonadal steroids (estradiol, testosterone) feedback on the LH cell and the DA neuron (and possibly on the kiss1 or kiss2 neurons). (Adapted with permission from Zohar, Y., et al., Neuroendocrinology of reproduction in teleost fish. General and Comparative Endocrinology 165, 438-455, 2010.) 41 Copyright © 2013 Elsevier Inc. All rights reserved.

42. Figure 5-39 The Kiss2–GnRH system in zebrafish brain. The zebrafish (Danio rerio) produces both kiss1 and kiss2, but only the latter has been linked to the regulation of GnRH release in the zebrafish. Abbreviations: EN, enteropeduncular nucleus; Hd, dorsal hypothalamus; Hv, ventral hypothalamus; P, pituitary; PI, pars intermedia; OB, olfactory bulb; POA, preoptic area; SR, superior raphe; TS, torus semicularis. (Adapted with permission from Servili, A. et al., Endocrinology, 152, 1527–1540, 2011.) 42 Copyright © 2013 Elsevier Inc. All rights reserved.

43. Figure 5-40 Phylogeny of CRH and CRH-like peptides. CRF = CRH; Danio, zebrafish; EurFl, European flounder; Gfish, goldfish; PSauv, Phylomedusa sauvageii; Rcates, bullfrog; Sckr, white sucker; Te, pufferfish; Til, tilapia; Xlaev, X. laevis; Xtrop, X. tropicalis. (Adapted with permission from Boorse, G.C. et al., Endocrinology, 146, 4851–4860, 2005.) 43 Copyright © 2013 Elsevier Inc. All rights reserved.

44. Figure 5-41 Corticotropin-releasing hormone (CRH) and the HPA–HPTaxes of amphibians. CRH acts as both a thyrotropin-releasing hormone and a corticotropin-releasing hormone in amphibians. The system is influenced by environmental factors acting through various neural centers that all feed information to the hypothalamus. (Adapted with permission from Denver, R.J., General and Comparative Endocrinology, 164, 20– 31, 2009.) 44 Copyright © 2013 Elsevier Inc. All rights reserved.

45. Figure 5-42 Nonapeptide preprohormones. Comparison of human AVP and OXY preprohormones with those of AVTand IST, respectively, from Japanese fugu, a teleost fish. See text for explanation of abbreviations. (Adapted with permission from Gwee, P.-C. et al., BMC Evolutionary Biology, 8, 93, 2008.) 45 Copyright © 2013 Elsevier Inc. All rights reserved.

46. Figure 5-43 Evolution of neurohypophysial nonapeptides genes. The letter “D” within the circle represents a gene duplication event. The numbers within the circles denote the position of the amino acid that has been substituted (shown above the circle). Note that the presence of MST and PYP in some marsupials has not been included. See text for an explanation of abbreviations. (Adapted with permission from Gwee, P.-C. et al., BMC Evolutionary Biology, 8, 93, 2008.) 46 Copyright © 2013 Elsevier Inc. All rights reserved.

47. Figure 5-44 The epiphysial complex. The pineal gland and associated structures are shown for a generalized teleost, frog, lizard, and mammal (rat). 1, skin; 2, skull; III, third ventricle. Abbreviations: CP, choroids plexus; DS, dorsal sac; E, epiphysis (pineal), H, habenular commissure; PA, parietal (parapineal) organ; PC, posterior commissure; PN, pineal nerve; PS, paraphysis; PT, pineal tract; SC, subcommissural organ; X, parietal nerve. (Adapted with permission from Bentley, P.J. “Comparative Vertebrate Endocrinology”, Cambridge University Press, 1976.) 47 Copyright © 2013 Elsevier Inc. All rights reserved.

48. Figure 5-45 Comparison of mammalian and non-mammalian melatonin systems. SCN, suprachiasmatic nucleus. See text for comparison. (Adapted with permission from Hazlerigg, D.G. and Wagner, G.C., Trends in Endocrinology and Metabolism, 17, 83–91, 2006.) 48 Copyright © 2013 Elsevier Inc. All rights reserved.

49. Figure 5-46 Changes in melatonin secretion patterns with seasonal changes in day length (hours of light) in a generalized teleost fish. Such changes have been associated with initiation of reproductive development in some species. (Adapted with permission from Bromage, N. et al., Aquaculture, 197, 63–98, 2001.) 49 Copyright © 2013 Elsevier Inc. All rights reserved.

50. Figure 5-47 Photoperiodic control of puberty/recrudescence and spawning in fishes. Photoperiod effects vary by season with respect to different reproductive events. These effects are modulated by permissive factors such as fish size at that time, nutritional status, water temperature, and rainfall (which can affect salinity, temperature, etc.). (Adapted with permission from Bromage, N. et al., Aquaculture, 197, 63–98, 2001.) 50 Copyright © 2013 Elsevier Inc. All rights reserved.

51. Table 5-5 GnRH Amino Acid Sequences. The chordate GnRHs are all decapeptides. Invertebrate GnRH-like peptides consist of 11 or 12 amino acids. (Adapted with permission from Roch, G.J., Busby, E.R., Sherwood, N.M. Evolution of GnRH: Diving deeper. General and Comparative Endocrinology 171, 1–16., 2011). 51 Copyright © 2013 Elsevier Inc. All rights reserved.