HORMONAL REGULATION: MORPHOGENETIC AND ADAPTIVE SYSTEMS

1. The endocrine glands of vertebrates develop from all three germ layers; those arising from ecto- and endoderm produce hormones of an amino-acid or polypeptide-type, while those arising from the mesoderm secrete hormones of a steroid nature. 2. All mesodermal glands and a single endodermal gland, the thyroid, are under hypophyseal control. 3. All pituitary-controlled endocrine glands act upon morphogenetic processes after a certain stage of phylogenesis, and the same applies to the directly-acting hypophyseal hormone STH. It follows that the pituitary acts not so much as the ‘conductor of endocrine glands’ in general, but as the central regulator of morphogenetic processes in particular. 4. Incorporation of the thyroid gland into the morphogenetic system took place at the phylogenetic level at which its morphogenetic role came to the fore in processes of metamorphosis. 5. The other main hormone system, the adaptive system, includes all endocrine glands of ecto- or endodermal origin. These account for short-term homeostatic regulation and depend on the pineal body for higher control. 6. While hypophyseal regulation is stimulatory and is operated through a precise feed-back mechanism, regulation by the pineal body is more primitive and inhibitory, with minimal indications of feed-back. The influence becomes stimulatory only in those instances in which the target glands are controlling the same function in an opposite manner, e.g. the parathyroid and the C-cell. The pineal influence also inhibits the function of the thyroid, and hypophyseal stimulation becomes superimposed on this inhibitory effect, in accordance with an actual requirement.     

Excretion, Metabolism and Enterohepatic Circulation Pathways and Their Role in Overall Thyroid Hormone Regulation in the Rat

Regulation of thyroid, adrenocortical and other hormones secretedby the major endocrine glands in mammals is widely attributedprimarily to feedback control relationships with the pituitary,hypothalamus or both, with hepatobiliary and intestinal mechanismshaving no more than a passive or excretory role. I present anotherview of enterohepatic components in thyroid endocrine function,suggesting a functional and more pervasive role for the intestine,in a more complex hierarchical system controlling thyroid hormonelevels, effects and economy in the rat, and possibly in othermammals. A central factor is the existence of enterohepaticcycling of these hormones, or their reabsorption from intestnalpools to portal and then systemic blood. This process affectstheir dynamic behavior throughout the organism, not only hormoneeconomy, because bidirectional transport of hormone betweenblood and intestine (including large pools in luminal contents)renders all or part of the gut internal to the system regulatingthyroid hormones. We review the evidence for and possible significanceof this hypothesis, covering specific aspects of hormone levelcontrol in the rat, including the deiodination, conjugationand other metabolic pathways, particularly in liver and intestine,and the fecal and urinary excretory (sink) and hormone production(source) pathways. The modulators of enterohepatic subsystemregulation of thyroid hormones are postulated to involve thecombined effects of hormone conjugation and degradation processesin liver and their subsequent secretion in bile, coupled withthe bacterial deconjugation, the reabsorption and certain hormonestorage mechanisms of the intestine.     

Widespread expression of zinc transporter ZnT (SLC30) family members in mouse endocrine cells

Zinc is abundant in most endocrine cell types, and plays a pivotal role in the synthesis and secretion of many hormones. Recent studies have demonstrated the expression of numerous zinc transporter (ZnT) family members in the pancreas, thyroid, and adrenal glands, suggesting a role for ZnTs in regulating cellular zinc homeostasis in endocrine cells. However, the cellular distribution of ZnTs in the endocrine organs has not been well established. In the present study, the mRNA expression level, cellular distribution of ZnTs as well as liable zinc ions were examined in the mouse pituitary, adrenal glands, thyroid, and pancreas. In general, ZnT1-10 mRNA was expressed to various degrees in the detected endocrine organs, with no detectable ZnT10 mRNA in the pancreas. In the anterior pituitary, both the acidophilic and basophilic cells were immunopositive to ZnT1-5, 7, 8, except for ZnT10. In the adrenal cortex, the immunoreactivity of all the tested ZnTs, including ZnT1-5, 7, 8, 10, was observed in the zona fasciculata, and some ZnTs were detected in the zona glomerulosa, zona reticularis, and the adrenal medulla. Both the follicle epithelial cells and parafollicular cells in the thyroid gland were immunostained with ZnT1-5, 7, 8, but not ZnT10. In the endocrine pancreas, the immunoreactivity of tested ZnTs was observed to various degrees except for ZnT10 in the cytoplasm of islet cells. Furthermore, autometallographic staining showed that liable zinc was observed in the endocrine cells, such as the adrenal cortical cells, thyroid follicle epithelial cells, and the pancreatic islet cells. All together, the wide distribution of liable zinc and the phenomenon that numerous ZnT family members are partially overlapped in a subset of endocrine cells suggest an important role for the ZnT family in controlling cellular zinc levels and subsequently regulating the synthesis and secretion of hormones in the endocrine system.     

Effect of alpha-tryptophan on conditioning and behavior in rats with experimental pathology of the thyroid gland

Effects of L-tryptophan on learning and behavior were studied in male rats with a deficit or excess of thyroid hormones. Learning was assessed in active avoidance paradigm, and behavior was estimated in the "open-field" test. It was found that L-tryptophan restored the capability of thyreoidectomized rats for acquisition and reproduction of the active avoidance reaction and increased the exploratory behavior of these rats in the open-field. In triiodothyronine treated rats, L-tryptophan eliminated a light stimulatory effects of thyroid hormones on the processes of formations and retention of the active avoidance reaction, increased the exploratory activity, but decreased grooming in the open-field.     

Expression of Secretogranin III in Chicken Endocrine Cells: Its Relevance to the Secretory Granule Properties of Peptide Prohormone Processing and Bioactive Amine Content

The expression of secretogranin III (SgIII) in chicken endocrine cells has not been investigated. There is limited data available for the immunohistochemical localization of SgIII in the brain, pituitary, and pancreatic islets of humans and rodents. In the present study, we used immunoblotting to reveal the similarities between the expression patterns of SgIII in the common endocrine glands of chickens and rats. The protein–protein interactions between SgIII and chromogranin A (CgA) mediate the sorting of CgA/prohormone core aggregates to the secretory granule membrane. We examined these interactions using co-immunoprecipitation in chicken endocrine tissues. Using immunohistochemistry, we also examined the expression of SgIII in a wide range of chicken endocrine glands and gastrointestinal endocrine cells (GECs). SgIII was expressed in the pituitary, pineal, adrenal (medullary parts), parathyroid, and ultimobranchial glands, but not in the thyroid gland. It was also expressed in GECs of the stomach (proventriculus and gizzard), small and large intestines, and pancreatic islet cells. These SgIII-expressing cells co-expressed serotonin, somatostatin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, or insulin. These results suggest that SgIII is expressed in the endocrine cells that secrete peptide hormones, which mature via the intragranular enzymatic processing of prohormones and physiologically active amines in chickens.     

Microtopographic relation between the lymphatic capillaries and glands of the small intestine

Microtopographic interrelationships of the lymphatic capillaries and glands of the small intestine have been investigated taking into account new data on the diffuse endocrine system, which includes endocrine cells of the gastro-intestinal tract. An immediate contact of the lymphatic capillaries with the intestinal glands, resembling microtopographic interrelationships of the lymphatic capillaries in the endocrine glands, has been revealed in total translucent and histological preparations. A suggestion is made that the microtopographic interrelationships of the lymphatic capillaries and the intestinal glands can be regarded as a morphologic basis for absorption of hormones produced by the endocrine cells of the intestinal glands.     

Morphometric structure of thyroid and adrenal glands in bulls under different modes of adaptive technology

This work was carried out to study dynamics of morphometric structure of thyroid and adrenal glands in bulls brought up in early postnatal ontogenesis at lowered (-4.4-(-)8.0 degree centigrade) and raised (8.7-20.5 degree centigrade) environment temperature with further grow and fattening using intensive technology with application of new biogenic matters. For the first time it has been experimentally proved the expediency of correction of morphometric structure of investigated endocrine glands in bulls under condition of joint application of Suvar with Polistim or with DAFS-25 during the various periods of postnatal ontogenesis. Special features of morphometric structures of the thyroid glands (diameter, the area of follicles, thickness of thyroid epithelium, follicles index) and the adrenal glands (weight, width of zones of cortical and brain substances, the areas of cells and nuclei, and nuclear cytoplasmic ratio) in animals maintained under condition of adaptive technology have been investigated. It has been established that the endocrine glands morphometric parameters in bulls brought up at both lowered and raised temperature are more relief under combined effect of Suvar and DAFS-25 than Suvar and Polistim.     

Neuroendocrine aspects of aging: experimental data

Aging is characterized by changes in neuroendocrine/endocrine functions which are manifest in female reproductive physiology and less perceptible in other functions such as thyroid, adrenal or growth/metabolic functions. The contribution of each level of the axis - hypothalamus, adenohypophysis or peripheral tissues - is not clearly established. Functional impairments with age are recognized in the peripheral glands (gonad, thyroid, adrenal) as well as in the pituitary, but increasing evidence is accumulating for a marked contribution of the hypothalamus in the age-associated endocrine changes observed in animals and humans. In old rats, multineuronal dysfunctions are demonstrated in the hypothalamus, with a documented decline in the activity of the neurons producing dopamine and thyrotropin-releasing hormone, and to a lesser extent luteinizing hormone- and growth hormone-releasing hormones, and alterations in regulatory mechanisms of these neurons are disclosed. Moreover, impairments are observed in the processing - binding, accumulation and intracellular distribution - of hypothalamic hormones in the adenohypophysis of old rats. Taken together, these observations are supportive of the view that the neuroendocrine/endocrine changes appearing with age result from a complex balance of functional alterations occurring at each level - central and peripheral - of the axis.     

Chromogranin A is present in and released by fish endocrine tissue

Chromogranin A (CgA) is a protein that is present in many mammalian endocrine cells and co-secreted with their resident hormones. We have demonstrated the presence of CgA by immunohistology in the ultimobranchial glands and corpuscles of Stannius of rainbow trout. CgA was also detected by radioimmunoassay in the medium of incubated coho salmon ultimobranchial glands. Our observations demonstrate the presence of CgA in endocrine glands of evolutionarily divergent species. These observations are consistent with the hypothesis that CgA participates in the secretory process of a wide variety of hormones.     

On the expression of cytokeratins and their distribution in some rabbit gland tissues.

The composition and distribution of cytokeratins were studied in a series of exocrine and endocrine glands in the rabbit, by means of anti-human monoclonal antibodies. Rabbit cytokeratins are known to be homologous to those in man, and their in situ distribution was also found to be similar. In acinic cells of the exocrine glands, only cytokeratins 8 and 18 were detected, whereas in ductal cells 1, 5, 10, 11 and 13, 19 were also present. The myoepithelial cells surrounding acini and basal duct cells were stained with the antibodies directed against cytokeratins 13 and 1, 5, 10, 11. Among the endocrine glands, a higher reactivity was observed in the thyroid gland and pancreatic islets, while pituitary and adrenal gland often remained unstained. Although the expression of cytokeratins was found to be almost homogeneous in each glandular cell type, a certain variability was observed, depending on the organ examined and the treatment carried out.     

Die Bedeutung der Hormone für die Temperaturanpassung im normalen Temperaturbereich

Experiments dealing with an influence of endocrine glands in oxygen consumption of poikilothermic vertebrates are briefly reviewed. In spite of the negative findings of other investigators, some results suggest an endocrine control of the ability of cold-blooded vertebrates to adapt their respiration to changing environmental temperature. However, if hormones play a role in stimulating oxidative metabolism, it would be expected that the metabolic rate of isolated tissues would reflect the capacity adaptation of intact animals. Experimental results do not confirm this expectation in all cases; furthermore, there is only little evidence that thyroid hormones increase thein vitro respiration. On the other hand, tissue respiration is stimulated by adding small quantities of blood taken from cold-adapted animals. Some aspects concerning hormone induced shifts in metabolic pathways are discussed.     

Endocrine control of Anguilla anguilla glass eel dispersal: effect of thyroid hormones on locomotor activity and rheotactic behavior

Dispersal, one of the most important processes in population ecology, is an issue linking physiological and behavioral features. However, the endocrine control of animal dispersal remains poorly understood. Here, we tested whether and how thyroid hormones may influence dispersal in glass eels of Anguilla anguilla, by testing their influence on locomotor activity and rheotactic behavior. Glass eels were caught during their estuarine migration and treated by immersion in either a l-thyroxine (T(4)) or a thiourea (TU) solution. As measured by radioimmunoassay, T(4) and TU treatments induced, respectively, increased and decreased whole-body thyroid hormone levels relative to untreated controls. We tested a total of 960 glass eels distributed into control, and T(4) and TU treatment groups, on their swimming behavior in experimental flume tanks equipped with upstream and downstream traps that allowed us to concurrently measure both the locomotor activity and the rheotactic behavior. Compared to controls, locomotor activity significantly increased among the hyperthyroid, T(4)-treated eels, but significantly decreased among the hypothyroid, TU-treated eels. The results on rheotactic behavior suggested a more complex regulatory mechanism, since TU but not T(4) treatment significantly affected rheotactic behavior. The influence of thyroid hormones on locomotor activity suggests a central role for these hormones in the regulation of mechanisms leading to the colonization of continental habitats by glass eels. Thyroid hormones are also implicated in the control of locomotor activity in mammals and migratory behavior in birds, suggesting that these hormones represent conserved, proximate mediators of dispersal in vertebrates.     

实验性脾虚证大鼠内分泌腺形态学与细胞化学研究

成年Ｗｉｓｔａｒ大鼠２０只,分对照组和实验组。实验组用大黄煎剂灌服４２天致实验性脾虚证。对两组睾丸,肾上腺和甲状腺进行常规形态学与细胞化学观察。形态学显示：睾丸,肾上腺和甲状腺的组织和细胞均有不同程度的损伤。细胞化学显示：各内分泌腺均表现酸性磷酸酶（ＡＣＰ）减弱,个别内分泌腺细胞显示琥珀酸脱氢酶（ＳＤＨ）,三磷酸腺苷酶（ＡＴＰａｓｅ）和ＰＡＳ反应的变化。结果证明脾虚证不仅消化系统功能低下,而且内分泌功能也受到了影响     

Effect of endocrine glands on the unfixed total haemocyte counts of the bug Halys dentata

Changes in total haemocyte counts in relation to the endocrine glands have been studied in Halys dentata. Unfixed total haemocyte counts were taken after extirpation and implantation of three endocrine structures. It is concluded that haemocyte count decreases after the extirpation of the corpora allata in the early life span of adults, while an abrupt increase was noted after the 7th day. When both the corpora allata and corpora cardiaca are extirpated, the count was significantly decreased throughout the life span of adults. However, when only the corpora cardiaca were removed there was no significant variation up to the 7th day, but later on the count gradually decreased. The implantation of brain, corpora cardiaca and allata is followed by a significant rise in the haemocyte count throughout the life span. Total haemocyte count also fluctuated after the implantation of corpora allata and brain, separately. After implantation of corpora cardiaca of one-day-old adult insects there was no variation in the total haemocyte count while the corpora cardiaca of 6-day-old adults when implanted in one-day-old adults cause a significant rise in the total haemocyte count. Therefore, it is concluded that the corpora cardiaca influences the total haemocyte count after a critical period.     

Neuro-steroids: 3β-hydroxy-Δ5-derivatives in the rodent brain

Pregnenolone, dehydroepiandrosterone and their sulfate esters have been characterized in the rat brain. Their formation or accumulation depend on in situ mechanisms unrelated to the peripheral endocrine glands. Although their functions are still poorly understood, they may affect the brain by metabolism to sex steroid hormones and they may be functionally related to sexual behavior, possibly through direct modulations of the firing rates of neurons.     

Noise Induces Hypothyroidism and Gonadal Dysfunction Via Stimulation of Pineal–Adrenal Axis in Chicks

Noise is a world-wide problem that causes nervous, endocrine and cardiovascular disorders, and eventually health hazards in humans and animals. Objective of the current work is to investigate endocrine interaction in noise stress, which subsequently affects other endocrine functions including gonads in a poultry bird like chicks. Gravimetric, ultrastructural and hormonal status of the endocrine organs were examined to ascertain the effects of noise stress. Acute noise at 60 dB had no effect, but at 80 and 100 dB each for 3 h, increased pineal and serum serotonin, and adrenal and serum corticosterone, epinephrine and norepinephrine concentrations, without any change in thyroid or gonadal hormones. Chronic noise exposure at 60, 80 and 100 dB each for 6 h, daily for 7 days, drastically disturbed normal behavior, and quantum of food consumption and water intake. Chronic exposure also significantly decreased body weight including thyroid, ovary and testis weight, and increased adrenal weight. Noise stress caused ultrastructural changes leading to stimulations of pinealocytes (with abundance of rough endoplasmic reticulum and mitochondria), adrenocortical cells (enlarged nuclei and abundance of smooth endoplasmic reticulum) and adrenomedullary cells (enlarged nuclei with presence of chromaffin granules) were observed in noise stress. Additionally, pineal and serum serotonin, N-acetyl serotonin and melatonin, and adrenal and serum corticosterone, epinephrine and norepinephrine levels were significantly elevated following chronic noise exposure. Contrarily, thyroid activity was suppressed with atrophied thyroid follicles followed by declined levels of serum T₃ and T₄ with elevation of TSH level. Simultaneously, serum 17β-estradiol (E₂) and testosterone (T) concentrations were also significantly declined in all the doses of chronic noise. These changes were dose dependent of noise exposure. The findings suggest that (a) adrenal and pineal glands respond primarily to noise and secondarily act on other endocrine organs including gonads in chicks, (b) adrenal directly and/or indirectly causes thyroid and gonadal dysfunctions via pineal following noise exposure in chicks.     

Dynamics of thyroid diseases and thyroid‐axis gland masses

Thyroid disorders are common and often require lifelong hormone replacement. Treating thyroid disorders involves a fascinating and troublesome delay, in which it takes many weeks for serum thyroid‐stimulating hormone (TSH) concentration to normalize after thyroid hormones return to normal. This delay challenges attempts to stabilize thyroid hormones in millions of patients. Despite its importance, the physiological mechanism for the delay is unclear. Here, we present data on hormone delays from Israeli medical records spanning 46 million life‐years and develop a mathematical model for dynamic compensation in the thyroid axis, which explains the delays. The delays are due to a feedback mechanism in which peripheral thyroid hormones and TSH control the growth of the thyroid and pituitary glands; enlarged or atrophied glands take many weeks to recover upon treatment due to the slow turnover of the tissues. The model explains why thyroid disorders such as Hashimoto''s thyroiditis and Graves'' disease have both subclinical and clinical states and explains the complex inverse relation between TSH and thyroid hormones. The present model may guide approaches to dynamically adjust the treatment of thyroid disorders.     

Thyroid gland function in ovariectomized ewes exposed to phytoestrogens

Phytoestrogens are by definition plant-derived substances that are able to activate the mammalian oestrogen receptors. We examined the possible effects of phytoestrogens on the secretion of thyroid hormones as well as on the immunoreactivity to oestrogen receptor alpha (ER alpha) in the thyroid glands of ovariectomized ewes. Eight ovariectomized ewes were fed 3.5 kg of 100% red clover silage for 14 days. Blood samples were collected before and on day 14 of exposure to phytoestrogens. After 5 months, four of the ewes were re-exposed to red clover silage as described above and the other four served as controls. Blood samples were collected as above. All ewes were slaughtered at the end of the experiment and the thyroid glands were weighed and examined for macroscopical changes. Tissue samples were taken for immunohistochemistry and image analysis. Ewes exposed to red clover silage had significantly higher plasma concentrations of total T(3) and free T(3) than ewes fed hay. The cross-section area of thyroid follicles tended to be larger in ewes fed red clover silage than in the control animals. ER alpha immunoreactivity was stronger in thyroid glands from ewes exposed to phytoestrogens than in ewes fed hay. In conclusion, daily ingestion of 81-95 mg phytoestrogens per kg body weight for 14 days stimulated secretion of thyroid hormones and tended to increase follicle size and ER alpha immunoreactivity of thyroid glands of ovariectomized ewes.     

Fine structure of the fetal rat thyroid and parathyroid glands at term and during prolonged gestation

Summary The fine structure of the fetal rat thyroid and parathyroid glands was studied at term and during prolonged gestation, which was induced by subcutaneous injections of progesterone to the mothers from gestational days 20 through 24. At term, the follicular and parafollicular cells of the thyroid as well as cells of the parathyroid exhibited well developed cytoplasmic organelles. Morphological changes were not detected in either of the endocrine glands during prolonged gestation. The results are discussed in relationship to 1) thyroid follicular cell activity during stress and 2) the function of thyroid parafollicular and parathyroid cells in calcium homeostasis.Supported by the Medical Research Council of Canada Grant No. MA4740.