Breaking Dogma on the Hypothalamic-Pituitary Anatomical Relations in Vertebrates.

The hypothalamus and pituitary are present in all vertebrates from agnathans (jawless fishes) to mammals. The hypothalamus is located below the thalamus, just above the brain stem and forms the ventral part of the diencephalon. The appearance of the pituitary was a seminal event in the evolution of vertebrates (1, 2). The pituitary is not present in protochordates or other invertebrates. The pituitary consists of the same 2 principal divisions, the neurohypophysis and adenohypophysis. The neurohypophysis develops from the floor of the diencephalon as an infundibular extension, whereas the adenohypophysis develops from the oral epithelium that comes in contact with this infundibulum. In vertebrates, the evolution of a complex pituitary with dual developmental origin along with the more highly developed tripartite brain added another layer of control leading to the neuroendocrine control of many complex physiological functions such as growth, reproduction, development and metabolism among others. These functionally adaptive conditions may then have contributed to the expansion of vertebrates into new environments. The acquisition of the vertebrate pituitary probably resulted from wholegenome duplications that occurred early in vertebrate evolution (3). The adenohypophysis of the pituitary gland secretes a number of protein hormones that regulates a variety of the physiological processes of vertebrates. The adenohypophysial hormones can be classified, on the basis of structural and functional similarity, into 3 groups, the proopiomelanocortin family, the GH/prolactin/somatolactin family, and the glycoprotein hormone family (gonadotropins, thyroid-stimulating hormone, and a novel hormone called thyrostimulin). Somatolactin is only found in teleosts. Each family is believed to have evolved from an ancestral gene by duplication and subsequent mutations (4). During the evolution of the vertebrates, structural features of the pituitary and hypothalamus also evolved that perhaps optimized the communication between these tissues as vertebrates became larger and more complicated in form and distance between the hypothalamus and pituitary increased significantly (5). Classically, in vertebrates, there are generally 3 models for anatomical control of the pituitary: portal system via the median eminence (tetrapods); direct innervation (teleosts) and diffusion (agnathans). In mammals, releasing hormones are secreted from the terminal boutons in the median eminence and enter the vascular portal network through capillary beds (6). The releasing hormones subsequently act on the glandular tissue of the adenohypophysis, or anterior pituitary, inducing the synthesis and release of the anterior pituitary hormones (6). Of all vertebrates, only the agnathan and teleosts lack a portal vascular system (median eminence) for transferring neurohormones from the hypothalamus to the adenohypophysis (7). The adaptive importance of such a portal system is that it makes possible central nervous regulation of such vital processes as reproduction by external (and internal) cycling environmental conditions. As extensively reported in the literature, the teleosts have solved this structural problem by direct innervation of the pars distalis by appropriate neurosecretory neurons from the adjacent hypothalamus (8). The agnathans (basal vertebrates), however, have no nervous or vascular communication between the brain and neurohypophysis (9). This had led to speculation that nervous regulation of the agnathan pars distalis is by diffusion of brain peptides from