Abstract
The modern views on the anatomical and physiological interactions between the hypothalamus, pituitary and thyroid gland have emerged only in the last fifty years, although their historical roots may be found in a number of ancient and still poorly known ideas and observations. The regulation of energy body stores and temperature by the hypothalamic-pituitary-thyroid axis, for example, is a classical case of “fixitèe du mileu interieur” in the sense originally suggested by Claude Bernard in the late 1800s, i.e. a homeostatic mechanism, but already 2100 year before Aristotle had stated that the brain was necessary for the maintenance of body integrity by regulating food intake and behavior in relation to body temperature, the latter primarily determined by the heat of the circulating blood. Five hundred years later Galen of Pergamon reported fundamental discoveries in the anatomy of the third ventricle region, including the location of the pituitary gland inside the sella turcica embodied in a vascular network, the rete mirabilis, and observed nerves adjoining the “soft flesh” in the neck, i.e. the thyroid gland. He first proposed that the energy of the body (the vital spirit) was carryed through the arteries at the level of the rete mirabilis, where it was transformed into nerve inpulse (the animal spirit), eventually tranferred by the nerves to the periphery of the body, “glands” included, raising implicitly the possibility for a nervous influence over the thyroid activity. The Galenic model remained virtually unaltered up to the beginning of the 14th century, when the mediaeval anatomist Mondino de' Liuzzi put forth the idea that the thyroid gland interacted with the heat of the blood circulating in the internal carotid arteries due to their anatomical relation with the thyroid. This interaction enriched the vital spirit, i.e. the energy of the body, prior to its “pituitary” transformation into animal spirit, i.e. to nerve inpulse directed to the periphery of the body. In addition, Mondino envisaged the possibility that the third ventricle was implicated in the regulation of the animal behavior by processing sensory, cognitive and emotional informations. No trace of these Mondino's ideas can be found throughout the Renaissance, despite the leading anatomical work of the period, the Fabrica by Andreas Vesalius, remained apparently prone to the Galenic dogma of the rete mirabilis. After Vesalius, the Galenic anatomy and physiology of the infundibular region survived for at least two more centuries, and we owe Luigi Galvani, the discoverer of animal electricity, the first detailed anatomical observation that in humans the nasal secretions were not a drainage waste of the brain ventricles, as postulated by Galen, but the product of nasal mucous glands. From an epistemological standpoint, Aristotle anticipated the possibility that the “set point” for energy intake and behavioral adaptation was determined by the interplay between the brain activity and a thermogenic principle present in the circulating blood, in a manner very close to a circuitry devoted to maintain the energetic and thermic stady state of the living organism (homeostasis). The Galenic modelling of brain-thyroid interaction is an evolution of the Aristotelian one, since it postulates an anatomical and functional loop linking the transport of body energy to the brain through the arteries, and the transformation of this energy into neural output directed to the peripheral glands, “thyroid” included, by the mediation of the pituitary gland. Finally, the proposal by Mondino de' Liuzzi provides a scheme of brain-thyroid interaction that merges together the “homeostatic” Aristotelian with the “pituitary/autonomic” Galenic models, suggesting that the thyroid plays a “thermoregulatory” role linked to the control of body energy. This remarkable set of ideas has never been credited to Mondino by the modern historical critique, possibly due to the impact that the methodological reform of anatomy by Vesalius, resulting in the denial of much Galenic tradition, had on the way to interpret Mondino's work from the late Renaissance up to the 20th century. The current concepts of the regulation by peripheral nerves of the thyroid blood flow and/or secretion seems to have been anticipated by anecdotal observations in the Egyptian and Roman times. In the second half of the 18th century the belief by Luigi Galvani that the peripheral nerves were carrying electrical impulses can be considered the first theoretical statement derived from an empirical evidence, i.e. the animal electricity, supporting the Galenic idea that autonomic fibers might influence the secretion of “humors” from peripheral glands, thyroid included. However, only during the last century and first half of the present one it is possible to recognize anatomical and physiological observations that, although controversial like those of W.B. Cannon on experimental hyperthyroidism, opened the way to the current evidence of an autonomic control of the thyroid function.
Similar content being viewed by others
References
Lechan RM, Toni R. Thyrotropin-releasing hormone (TRH) neuronal systems in the central nervous system. In: Nemeroff CB, ed. Neuroendocrinology. Boca Raton: CRC Press, 1992: 275–326.
Akal H, Campeau S, Cullinam WE, Lechan RM, Toni R, Watson SJ, Moore RY. Neuroendocrine systems I: Overview—thyroid and adrenal axis. In: Zigmond M, Bloom F, Landis S, Roberts J, Squire L, eds. Fundamental Neuroscience. San Diego: Academic Press, 1999: 1127–1150.
Toni R, Lecham RM. Neuroendocrine regulation of thyrotropin-releasing hormone (TRH) in the tuberoinfundibular system. J Endocrinol Invest 1993;16:715–753.
Andersson E, Haymaker W. Breakthroughs in hypothalamic and pituitary research. Prog Brain Res 1974;41:1–60.
Swanson LW. The hypothalamus. In: Bjorklund A, Hokfelt T, Swanson LW, eds. Handbook of Chemical Neuroanatomy, vol. 5: Integrated Systems of the CNS, Part I, Hypothalamus, Hippocampus, Amygdala, Retina. Amsterdam: Elsevier, 1987: 1–124.
Harris GW, ed. Neural Control of the Pituitary Gland. London: Arnold, 1955.
Greer MA.Evidence of hypothalamic control of the pituitary release of thyrotrophin. P Soc Exp Biol Med 1951;77:603–608.
Brown-Grant K, Harris GW, Reichlin S. The effect of the pituitary stalk section on the thyroid function in the rabbit. J Physiol (Lond) 1957;136:364–379.
Szentagothai J, Flerkò B, Mess B, Halasz B, eds. Hypothalamic Control of the Anterior Pituitary. An Experimental-Morphological Study, 3rd rev. enlarged ed. Budapest: Akademiai Kiadò, 1972: 156–219.
Sawin CT. Defining thyroid hormone: its nature and control. In: McCann SM, ed. Endocrinology. People and Ideas. New York: Oxford University Press, 1988: 149–199.
Reichlin S. TRH: Historical aspects: Ann NY Acad Sci 1989;553:1–6.
Guillermin R, Burgus R, Sakiz E, Ward DN. Nouvelle doneès sur la purification de l'hormone hypothalamique TSH-hypophysiotrope, TRF.CRAcad Sci 1966;262:2278–2280.
Schally AV, Bowers CY, Redding TW, Barret JF. Isolation of thyrotropin releasing factor (TRF) from porcine hypothalamus. Biochem Biophys Res Co 1966;25:165–169.
Cannon WB, ed. The Wisdom of the Body. New York: W.W. Norton & Co., Inc., 1960.
Lanza D, Vegetti M, eds. Opere Biologiche di Aristotele, 2nd ed. Torino: UTET, 1996: 586–634.
Garofalo I, ed. Galeno, Procedimenti Anatomici. Milano: Rizzoli, 1991.
May MT, ed. Galen, On the Usefulness of the Parts of the Body, De Usu Partium. Ithaca, New York: Cornell University Press, 1968: 424–461.
Neuburger M, ed. Geschichte Der Medizin, Zwei Bande, I Band. Stuttgart: Verlag, 1906.
Garofalo I, Vegetti M, eds. Opere Scelte di Galeno. Torino: UTET, 1978: 784–822.
Medvei VC, ed. The History of Clinical Endocrinology. New York: Parthenon Publishing Group, 1993.
Giorgi PP, Pasini GF, eds. Anothomia di Mondino de' Liuzzi da Bologna, XIV Secolo. Bologna: Istituto per la Storia dell'Università di Bologna, Opere dei Maestri, vol. V, 1992.
Galvani L. Disquisitiones Anatomicae circa membranam pituitariam. In: Accademia delle Scienze dell'Istituto di Bologna, ed., Opere Edite ed Inedite di Luigi Galvani. Bologna: Accademia delle Scienze dell'Istituto di Bologna, 1998: 439–448.
Melander A. Autonomic nervous control: adrenergic, cholinergic, and peptidergic regulation. In: Braverman LE, Utiger RD, eds.Werner and Ingbars' The Thyroid,A Fundamental and Clinical Text, 5th ed. Philadelphia: Lippincot, 1986: 331–338.
Bryan CP, ed. The Papyrus Ebers. Translated from the German version, with an introduction by Smith GE. London: Geoffrey Bles, 1930: 151–157.
Watterson B, ed. Women in Ancient Egypt. New York: St. Martin's Press, 1991: 73–93.
Labbè M, Tinel J, Doumer E. Crises solaires et hypertension paroxistique en rapport avec une tumeur surrènale. B Soc Mèd Hop Paris 1922;46:982–990.
Barnett AJ, Blacket RB, Deporter AE, Sanderson PH, Wilson GM. Action of noradrenaline in man and its relation to phaeochromocytoma and hypertension. Clin Sci 1950;9:151–179.
Mowbray JF, Peart WS. Effects of noradrenaline and adrenaline on the thyroid. J Physiol (Lond) 1960;151:261–271.
Green JD. Neural pathways to the hypophysis: anatomical and functional. In: Haymaker W, Anderson E, Nauta WJH, eds. The Hypothalamus. Springfield: Charles C Thomas, 1969:276–310.
Tegler L, Gillquist J, Anderberg B, Jacobson G, Lundstrom B, Ross P.Human thyroid blood flow response to endogenous, exogenous human, and bovine thyrotrophin measured by electromagnetic flowmetry. Acta Endocrinol (Copen) 1981;98:540–548.
Mac Cormac W, ed. Surgical operations. The Ligature of Arteries, Part I. A Short Description of the Surgical Anatomy and Modes of Tying the Principal Vessels. London: Smith Elder and Co., 1885.
Hennemann G. Historical aspects about the development of our knowledge of morbus Basedow. J Endocrinol Invest 1991;14:617–624.
Cannon WB, Binger CAL, Fitz R. Experimental hyperthyroidism. Am J Physiol 1915;36:363–364.
Giannoni A. Semeiotica e diagnostica speciale delle malattie delle ghiandole endocrine. In: Sisto P, ed. Semeiotica e Diagnostica Medica. Torino: Minerva Medica, 1941: 1236–1339.
Hurwitz DJ, Rabson JA, Futrell JW. The anatomic basis for platysma skin flap. Plast Reconstr Surg 1983;72:302–315.
Legradi G., Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppresion of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 1997;138 (6):2569–2576.
Toni R, Ruggeri F, Briganti F, Lechan RM. The concept of hypothalamic integration in the “Anothomia of Mondino dei Liuzzi da Bologna.” Abstracts 26th Annual Meeting of the Society for Neuroscience, Washington DC, November 16–21, 1996;22(1):243.
Lechan RM, Toni R. Regulation of pituitary function. In: Korenman SG, ed. Atlas of Clinical Endocrinology, vol. 4. Philadelphia: Current Medicine, 2000: 1–25.
Saunders JB, O'Malley CD, eds. The Illustrations from the Works of Andreas Vesalius of Brussels. Cleveland: World Publishing, 1950: 186–199.
Roberts KB, Tomlinson JDW, eds. The Fabric of the Body. European Traditions of Anatomical Illustration. Oxford: Clarendon Press, 1992: 69–124
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Toni, R. Ancient Views on the Hypothalamic-Pituitary-Thyroid Axis: An Historical and Epistemological Perspective. Pituitary 3, 83–95 (2000). https://doi.org/10.1023/A:1009953723963
Issue Date:
DOI: https://doi.org/10.1023/A:1009953723963