Goiter in the court of the Byzantine Empress, Theodora.
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Art↗
Biomedical subjects
R Toni
Publications and source records attributed to R Toni.
Effects of hypothyroidism and endocrine disruptor-dependent non-thyroidal illness syndrome on the GnRH-gonadotroph axis of the adult male rat.
Effects of primary hypothyroidism (HYPO) on the male gonadal axis are controversial, with only scanty data on the gonadotroph cell response and no information on GnRH tuberoinfundibular neurons, even in animal models. HYPO has been reported to variably induce hypogonadotropic hypogonadism, a hypergonadotropic state, or to have no effects on basal levels of pituitary gonadotropins, both in adult male rats and humans. Similarly, the exogenous administration of GnRH to HYPO rats and humans may increase or decrease gonadotropin secretion. Since inhibitory effects of HYPO on the GnRH-gonadotropin axis are reversed by replacement with L-T4, it has been suggested that thyroid hormone (TH) may regulate tuberoinfundibular GnRH and pituitary gonadotropin biosynthesis and/or secretion. To shed light on this hypothesis, we conducted immunocytochemical studies on the distribution and immunostaining characteristics of hypophysiotropic GnRH neurons, LH, PRL and vasoactive intestinal polypeptide (VIP) immunoreactive (IR) cells in the pituitary of adult, male rats. We show that HYPO reduces IR-GnRH in a restricted population of tuberoinfundibular perikarya and their proximal axons compared to euthyroid controls, but increases IR-VIP both in pituitary cells in direct association with LH-gonadotrophs and within IR-LH cells, itself. We propose that VIP may serve as a juxtacrine/paracrine/autocrine regulator of LH secretion and that, when GnRH biosynthesis is reduced by HYPO, gonadotropin secretion may be rescued by local activating effects of VIP. Polychlorinated biphenyls (PCB), industry toxicants found in food and water, also have inhibitory effects on the gonadal axis, decreasing fertility and suppressing basal and GnRHinduced LH release in male rats. Since PCB may also exert endocrine disruptor-dependent (EDD) effects on the thyroid axis producing a non-thyroidal illness syndrome (NTIS) (coined EDD-NTIS), we developed a rat model of EDD-NTIS to determine whether central hypothyroidism may contribute to the pathophysiology of PCB-induced hypogonadism. On the basis of preliminary animal data, we speculate that one of the mechanisms for Partial Androgen Deficiency of the Aging Male may involve central hypothyroidism and EDD-NTIS, resulting in inhibition of the GnRH-gonadotroph axis.
Animals↗
New paradigms in neuroendocrinology: relationships between obesity, systemic inflammation and the neuroendocrine system.
Obesity may be an independent risk factor for coronary artery disease and contribute to a chronic state of systemic inflammation leading to atherosclerosis and metabolic abnormalities, such as diabetes, insulin resistance, dyslipidemia and hypertension. Visceral fat, in fact, may act as an endocrine organ, synthesizing and releasing atherogenic inflammatory cytokines, whose circulating levels depend on the individual's nutritional state, and the extent and anatomical location of fat stores. Unsuspected viral infections might also be involved in enhancing autocrine/paracrine mechanisms of cytokine release from omental fat. Elevated levels of blood cytokines may interact with the neuroendocrine system, autonomic nerves and peripheral lymphatic organs. This may lead to local inflammatory reactions in many body compartments, in particular in the heart tissue, possibly affecting the process of circulatory recovery in obese subjects, and predisposing these patients to a greater risk of myocardial inflammatory disease than individuals with normal body mass index. Circulating levels of inflammatory cytokines might be considered to determine risk categories for development of cardiovascular complications in obese subjects. In addition, their reduction with pharmacological antagonists might prevent and/or control acute cardiovascular events and increase energy expenditure in obese patients, especially after surgical treatment, through reduction of cytokine inhibition of the hypothalamic-pituitary-thyroid axis.
Adipocytes↗
The neuroendocrine system: organization and homeostatic role.
The neuroendocrine system (NES) of Vertebrates can be defined as a set of cells organized in single organs and diffuse elements, sharing co-production of amine hormone/transmitters, peptide hormone/transmitters and specific markers of neural determination. In this perspective, the hypothalamic-pituitary-target organ axis (H-P axis), the autonomic nervous system (ANS) and the diffuse neuroendocrine or APUD system contribute to the NES. However, in Mammals and man virtually any compartment of the body harbors elements, often with different embryologic origin, having at least some of the NES features. Thus, all anatomical structures may be part of a wide functional circuitry, based on "internal secretions", that supersedes the current view of the NES. Historically, metaphysical antecedents of this concept can be found in the biomedical tradition dealing with the idea of the so called "vital energy". Currently, the "internal secretions" circuitry can be envisaged as an informational supersystem encompassing the H-P axis, ANS, APUD, immune and any other body system performing autocrine, paracrine and/or endocrine regulations, that superintends the homeostatic balance. Evolutionary evidence shows that diffuse autocrine/paracrine/endocrine, peptidergic secretions would be the oldest and hierachically simplest signals, with respect to the later and hierarchically more complex ANS and H-P axis outputs, to regulate body homeostasis. Therefore, the new acronym "Triune Information Network" (TIN) is proposed for the informational supersystem of internal secretions acting in Mammals and man via progressively higher levels of control (diffuse autocrine/paracrine/endocrine secretions, ANS and H-P axis) on a common energetic substrate: the internal body milieu.
History, Ancient↗
The human hypothalamus: a morpho-functional perspective.
Historical investigation suggests that the role of the hypothalamus as a site of integration for endocrine with autonomic and behavioral responses in man rises from ideas and observations first appearing between the 14th and 18th centuries. Research on human, post-mortem brains and by in vivo magnetic resonance techniques reveal that the functional morphology of the hypothalamus in man is very similar to that in Rodents and Primates. As such, the adult human hypothalamus can be subdivided in three longitudinal zones, representing the source and target of neural informations traveling back and forth the brain stem, thalamus, limbic system, basal ganglia and neocortex. In addition, the human hypothalamus can be further partitioned in three anterior-posterior regions, of which the rostral one exerts a prominent regulation in predictive homeostasis, as opposed to the two caudal ones, primarily involved in reactive homeostasis. Finally, nuclear distribution in the human hypothalamus largely coincides with that in higher Mammals. Nevertheless, it is still unclear how the hypothalamus may give rise to specific homeostatic behaviors like hunger, thirst, reproductive and parental attitude, thermoregulation, aggressive-defensive performance, affective-motivational tone, circadian rhythmicity, sleep-wake cycle and immune regulation. The recent advent of new theories for nervous communication, like volume transmission and neural Darwinism, is progressively enlightening our understanding of the role played by the hypothalamic architecture in homeostatic responses, both in Mammals and man.
Afferent Pathways↗
Molecular mechanisms for pituitary thyrotroph cell growth.
Neuroendocrine, endocrine and autocrine/paracrine signals contribute to the regulation of basal thyrotroph growth. Thyrotropin-releasing hormone (TRH), somatostatin, thyroid hormone (TH), estrogens (Es) and epidermal growth factor, all may play a role both in normal and tumoral thyrotroph proliferation, acting via either plasma membrane receptors and non-genomic steps or nuclear receptors and gene transcription. Signaling features common to all these ligands are involvement of G protein-coupled receptors, mitogen-activated protein kinase cascade and nuclear polyphosphoinositide cycle. In addition, each growth information, independently from the eliciting factor, may be routed intracellularly following a branched pathway, that often links different transduction systems at common check-points, as the Shc-Grb2-SOS complex. Finally, some ligands (e.g. TRH, TH, Es) may display opposite effects on thyrotroph growth, depending on environmental conditions and state of cell differentiation. These ambiguities of response can be interpreted using a "fuzzy" logic-based model of intracellular signaling. Accordingly, check-points common to different transduction cascades may be envisaged as targets for antitumoral therapy selective to the neoplastic thyrotroph cell.
Animals↗
Endocrinology and art. Saint Onofrio.
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Disorders of Sex Development↗
Ancient views on the hypothalamic-pituitary-thyroid axis: an historical and epistemological perspective.
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 not widely 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 "fixitè du mileu interieur" in the sense originally suggested by Claude Bernard in the late 1800s, i.e. a homeostatic mechanism, but already 2100 year previously 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 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 carried through the arteries at the level of the rete mirabilis, where it was transformed into nerve impulse (the animal spirit), eventually transferred 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 present 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 transformation into animal spirit, i.e. to nerve impulse 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 inclined 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 blood, in a manner very close to a circuitry devoted to maintain the energetic and thermic steady 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. (ABSTRACT TRUNCATED)
Animals↗
The role of flow cytometry in the study of cell growth in the rat anterior pituitary gland.
Flow cytometry is a suitable technique for studying in vivo and in vitro the cell cycle kinetics of different animal and human tissues, both in normal and tumoral conditions. The rat anterior pituitary gland is a model to investigate cell growth and replication of differentiated, neuroendocrine cells, and we report current evidence on its cell cycle kinetics as well as on the role played by flow cytometry in this type of study. The proliferation potential of normal anterior pituitary cells is related to a number of different conditions, including heterogeneity of cell types, age and sex of donors, and circadian influences. In addition, the trend of cell proliferation in both in vivo and in vitro studies is similar, suggesting that cultured anterior pituitary elements may, at least in part, retain growth features analogous to those of the intact gland. Sorting of selective cell types and analysis of the relation between proliferating anterior pituitary cells and the light-dark cycle have shown that flow cytometry may be useful to investigate the replication process of the gland. By using a combination of flow cytometry, light microscopic immunocytochemistry and morphometry, we have reported a peculiar trend of proliferation in primary monolayer cultures of rat anterior pituitary gland, characterized by a non-linear reduction in their proliferation rate with advancing age, primarily dependent on a reduced transition of cells from the G0/G1- to the early S-phase pool. These studies indicate that flow cytometry offers insights into cell cycle check points of anterior pituitary cells, and suggest that it might be applied to the study of growth of selective pituitary elements, both in normal and tumoral conditions.
Animals↗
Acromegaly and intestinal neoplasms.
Acromegalic subjects show increased frequency of neoplastic lesions in the colon and rectum with respect to the general population. Recent prospective studies using colonoscopy have shown a 3 time higher prevalence of intestinal polyps and up to 4 time increased presence of colorectal cancer in acromegaly, independently of sex, age, duration of disease and clinical status of the patients. The polyps are distributed throughout the extension of the large bowel and are often multiple, showing at least two different histologic types: hyperplastic and adenomatous. Sometimes they are associated with intestinal carcinomas. Pancolonoscopy is the procedure of choice for the diagnosis of large bowel neoplasms, even though it may be difficult to complete in these subjects because of the frequent presence of an enlarged and elongated colon. It shows a higher sensitivity and specificity compared to other tests such as the barium enema, fecal occult blood test and serum levels of carcinoembryonic antigen. Therefore, it is recommended to follow up acromegalic patients using pancolonoscopy to obtain early detection of neoplastic lesions in the large bowel.
Acromegaly↗
Quantitative clinical anatomy of the human cornea in vivo. A morphometric study by ultrasonic pachymetry and computer-assisted topographic videokeratoscopy.
The cornea is the most important refractive element in the human ocular system, providing approximately two thirds of the eye's refractive power in the nonaccommodative state. The methods of description and analysis of the corneal anatomy in vivo continue to be refined thanks to the increased interest aroused by the advent of corneal refractive surgery, which aims to modify the dioptric power of the ocular system by altering the thickness and the radius of curvature of the cornea. In the present study we report quantitative morphometric data of corneal thickness and the radius of curvature of the anterior surface of the cornea obtained in vivo from normal human subjects using ultrasonic pachymetry and computer-assisted topographic videokeratoscopy. We found a highly significant statistical correlation in the distribution of corneal thickness and the radius of curvature of the anterior surface of the cornea along the principal corneal meridians (horizontal and vertical meridians) and within three different concentric zones of the cornea, 2, 4 and 6 mm, respectively, from the geometric center along the principal meridians. Correlation was also found for the same morphometric parameters between the right and the left eye. By contrast, no correlation was found between corneal thickness and the radius of curvature of the anterior surface of the cornea. These findings suggest that the adult human cornea is a structure characterized by a highly ordered tridimensional architecture and symmetry and that a specific distribution of corneal thickness and the radius of curvature of the anterior corneal surface along the principal meridians may be essential for the refractive function of the human corneal diopter in vivo.
Adult↗
Effect of hypothyroidism on vasoactive intestinal polypeptide-immunoreactive neurons in forebrain-neurohypophysial nuclei of the rat brain.
We have recently reported that hypothyroidism increases immunoreactive (IR)-vasoactive intestinal polypeptide (VIP) and VIP mRNA content in both parvocellular and magnocellular neurons of the rat, hypothalamic paraventricular nucleus (PVN). As VIP can stimulate vasopressin (AVP) secretion, we conducted an anatomical investigation to determine whether VIP-containing neurons in other regions of the brain that are involved with homeostatic mechanisms of water and salt conservation are also affected by hypothyroidism. The distribution and intensity of VIP immunostaining in neurons and fibers of the magnocellular-neurohypophysial system, including the hypothalamic PVN, supraoptic nucleus (SON) and accessory magnocellular cell groups, circumventricular subfornical organ (SFO), preoptic and anterior hypothalamus, midline thalamus, subthalamic zona incerta and posterior septal nuclei were studied using a highly sensitive immunocytochemical technique and unbiased neuronal counting methods, based on the optical dissector principle. Hypothyroidism increased the intensity of VIP immunostaining and/or the number/section, percentage and numerical density of IR-VIP neurons in the PVN, SON, nucleus circularis, periventricular preoptic nucleus of the hypothalamus and SFO. In addition, IR-VIP perikarya and/or fibers in the hypothalamic medial preoptic area and anterior periventricular nucleus, nucleus reuniens of the thalamus and dorsal fornix-triangular septal nucleus complex were also apparent in the hypothyroid animals while no immunostaining was seen in these areas in control animals. No quantitative and/or qualitative modifications in IR-VIP neurons and fibers were noted in the anterior hypothalamic area, suprachiasmatic nucleus, thalamic paraventricular nucles an subthalamic zona incerta between hypothyroid and control animals. These findings suggest an inverse relationship between thyroid hormone and VIP content and/or distribution of IR-VIP neurons in specific forebrain regions involved in the control of AVP release, extracellular fluid volume, thirst, blood pressure and anterior pituitary secretion. This raises the possibility that changes in fluid homeostasis and cardiovascular function occurring in hypothyroidism may be mediated, at least in part, by VIP-producing neurons in diverse regions of the brain.
Animals↗
Neuroendocrine regulation of thyrotropin-releasing hormone (TRH) in the tuberoinfundibular system.
[...] It is now required to list each part needed for mucous excretion. They are two ducts in the brain substance, then a thin portion of membrane shaped as the infundibulum, then the gland that receives the tip of this infundibulum and the ducts that drive the mucus (pituita) from this gland to the palate and nares. [...] and I said that one (duct) [...] from the middle of the common cavity (third ventricle) descends [...] into the brain substance, and the end of this duct is [...] the sinus of the gland where the brain mucus is collected [...].
Amino Acids↗
Hypothyroidism increases vasoactive intestinal polypeptide (VIP) immunoreactivity and gene expression in the rat hypothalamic paraventricular nucleus.
Vasoactive intestinal polypeptide (VIP) is produced by neurons in the rat hypothalamic paraventricular nucleus (PVN) and may have an important role as a prolactin-releasing factor. Recent work from our laboratories has shown that thyroid hormone regulates the content of VIP and VIP mRNA in the rat anterior pituitary, but its effect on VIP in the PVN is not known. To determine whether thyroid hormone alters VIP biosynthesis in the PVN, we studied the effect of hypothyroidism on the content of immunoreactive (IR)-VIP and VIP mRNA in PVN neurons using histochemical techniques. By immunocytochemistry, only scattered IR-VIP fibers were present in the PVN of control animals whereas IR-VIP perikarya and fibers were present in hypothyroid rats. By in situ hybridization histochemistry, no labeled neurons were recognized in the PVN in control animals whereas PVN neurons were labeled in hypothyroid rats. These findings raise the possibility that hypothyroidism exerts negative feedback regulation on VIP-producing neurons in the PVN and suggest that this may be important to modulate the stimulatory effects of VIP on anterior and/or posterior pituitary function.
Animals↗
Immunoreactive interleukin-1 beta localization in the rat forebrain.
To determine whether the cytokine, interleukin-1 beta, is present in the rat brain as has been reported in human brain, immunocytochemical studies were performed using an antiserum that recognizes recombinant, rat IL-1 beta. Immunoreaction product was present in the periventricular and medial hypothalamus, mossy fiber distribution in the hippocampus and olfactory tubercle. These studies demonstrate that IL-1 beta is part of a diffuse intrinsic neural system in the rat central nervous system, associated with regions involved with hypophysiotropic, autonomic, limbic and extrapyramidal functions.
Animals↗
Thyrotropin-releasing-hormone-immunoreactive innervation of thyrotropin-releasing-hormone-tuberoinfundibular neurons in rat hypothalamus: anatomical basis to suggest ultrashort feedback regulation.
Thyrotropin-releasing-hormone (TRH)-synthesizing neurons in the medial and periventricular parvocellular subdivisions of the rat hypothalamic paraventricular nucleus (PVN) are involved in regulation of the anterior pituitary. Since ultrashort feedback regulation of TRH in the hypothalamus has been suggested by physiological studies, we sought to identify the presence of TRH synaptic contacts containing TRH on TRH tuberoinfundibular neurons in the PVN. An immunocytochemical study was performed at light- and electron-microscopic levels using antiserum directed to the N-terminal cryptic sequence of the TRH precursor, preproTRH 25-50. At the light-microscopic level, contacts between TRH immunoreactive (IR) fibers and the perikarya and processes of TRH-IR neurons were observed in medial and periventricular subdivisions of the PVN. At the ultrastructural level, TRH-neurons appeared either tightly juxtaposed to TRH-immunopositive perikarya and dendrites or to establish axodendritic and axosomatic contacts suggestive of synaptic associations. These data provide a morphologic basis to support a neuroendocrine role for TRH or processed forms of proTRH in the PVN and in particular suggest their involvement as neuromodulators in an ultrashort feedback regulation of TRH tuberoinfundibular neurons.
Animals↗
1-naphthol-pyronin B as a novel substrate for silver intensification: application to light and electron microscopic immunocytochemistry of neuroendocrine systems.
We describe a modification of silver intensification of immunoperoxidase end-product using 1-naphthol (1N) and 1N enhanced by pyronin B after suppressing nonspecific tissue argyrophilia with a solution of penicillamine and merthiolate buffered near neutral pH. This approach facilitates the preservation of a second antigen sequentially labeled in the same tissue section for light microscopic double immunolabeling experiments and also allows retention of ultrastructural detail. Using this protocol, we obtained rapid and uniform silver intensification of somatostatin (SRIF)-immunoreactive (IR) neuronal perikarya and processes in the rat hypothalamic paraventricular nucleus (PVN). Ultrastructurally, 1N- and 1N-pyronin B-silver intensified reaction product was clearly recognized by the presence of a coarse intracellular precipitate of high electron density. Light microscopic double-immunolabeling studies demonstrated the association between SRIF- and thyrotropin-releasing hormone (TRH)-IR neuronal systems in the PVN. We propose that silver intensification of 1N and 1N-pyronin B is a useful alternative to standard methods of silver intensification of immunoperoxidase reaction product at both light and ultrastructural levels and may be particularly amenable for double-immunolabeling studies.
Animals↗