Ghrelin-stimulation test in the diagnosis of canine pituitary dwarfism

This study investigated whether ghrelin, a potent releaser of growth hormone (GH) secretion, is a valuable tool in the diagnosis of canine pituitary dwarfism. The effect of intravenous administration of ghrelin on the release of GH and other adenohypophyseal hormones was investigated in German shepherd dogs with congenital combined pituitary hormone deficiency and in healthy Beagles. Analysis of the maximal increment (i.e. difference between pre- and maximal post-ghrelin plasma hormone concentration) indicated that the GH response was significantly lower in the dwarf dogs compared with the healthy dogs. In none of the pituitary dwarfs, the ghrelin-induced plasma GH concentration exceeded 5 microg/l at any time. However, this was also true for 3 healthy dogs. In all dogs, ghrelin administration did not affect the plasma concentrations of ACTH, cortisol, TSH, LH and PRL . Thus, while a ghrelin-induced plasma GH concentration above 5 microg/l excludes GH deficiency, false-negative results may occur.     

The evaluation of hormone and metabolite profiles after the infusion of glucose, propionate and butyrate in cattle

Lactational performance in high-yielding dairy cows has its limits in metabolic processes. Energy metabolism is maintained by mobilization of body reserves via hormonal regulation, resulting in lipolysis and sometimes ketoacidosis. For characterization of such conditions the intraruminal and intravascular application of glucose and volatile fatty acids was used in ruminant physiology. On the other hand the results of such experiments were correlated to actual and potential milk yield. For this investigation pairs of monozygous Holstein Friesian twins were tested as heifers and as cows by intravenous infusion of glucose, propionate and butyrate after 18 hours of feed withdrawal. Insulin, growth hormone, glucose, free fatty acids and beta-hydroxybutyrate were measured before, during and up to 4 hours after infusion of substrates. Each substrate caused a transient change in plasma concentrations of metabolites and hormones. Differences between heifers and cows are discussed with the time series of the mean concentrations. The reaction profile of each animal was characterized by different parameters. Analysis of these parameters revealed a close relation between hormones and metabolites even under the conditions of the load-test.     

Avian reproductive endocrinology.

Hypothalamic-releasing factors regulate the secretion of anterior pituitary hormones. The anterior pituitary gland secretes the same six hormones as found in mammals: FSH, LH, prolactin, GH (somatotropic hormone), ACTH, and TSH, plus the melanotropic hormone. The endocrine hormones of the avian posterior pituitary gland concerned with reproduction are mesotocin and AVT. The pineal gland, through the secretion of the hormone melatonin, modulates the periodic autonomic functions of the central nervous system. The ovary produces estrogens, progestogens, and androgenic compounds. The testes produce testosterones and progesterone. The thyroid glands produce two hormones, T4 and T3. The avian adrenal glands produce corticosterone and aldosterone. The bursa of Fabricius is considered an endocrine organ since it is involved in the production of humoral factors. The male reproductive system undergoes hormonal changes associated with puberty, the breeding season, and molt. Some avian species undergo a type of disintegration and seasonal reconstruction of the testis and epididymis. The relationship of the ovarian follicular hormones and the plasma hormones varies depending on the stage of the reproductive cycle and the seasonal photostimulation. Female birds may conceive in the absence of a mate as a result of the fertile period phenomena. The blood chemistry of laying birds is different from that seen in nonlaying hens. Domestication has had a definite influence on the hormone cycles of some avian species. This may lead to certain reproductive problems.     

Calcium homeostasis and intact plasma parathyroid hormone during exercise and training in young Standardbred horses

Physical exercise is known to affect calcium homeostasis in horses, but there is little information on the hormonal regulation of calcium metabolism during exercise. In order to evaluate the effects of exercise and training on calcium homeostasis and intact plasma parathyroid hormone, 7 untrained Standardbred horses were studied in a 6 week training programme. These horses were accustomed to running on the treadmill 3 weeks before onset of training and were exercised on a high-speed treadmill with an initial incremental standardised exercise test (SET 1: 6 incremental steps of 5 min duration each; first step 5 m/s, increase 1 m/s). SET 1 was followed by a lactate-guided training programme (6 weeks in total) with 2 types of exercise in alternating order with a day of rest after each work day: high-speed exercise (HSE) of 15 min duration, starting at VLa4, continuous increase in speed every 60 s by 0.3 m/s (14 incremental steps); and low-speed exercise (LSE) at a constant velocity at VLa2.5, duration approximately 60-90 min. The whole training programme consisted of 8 HSE and 8 LSE sessions. HSE and LSE were calculated to require the same energy expenditure. A final SET (SET 2) finished the training programme. Blood samples for lactate, plasma total calcium [Ca], blood ionised calcium [Ca2+], blood pH, plasma inorganic phosphorus [P(i)] and plasma intact parathyroid hormone [PTH] were collected before, during and after SETs 1 and 2, before and after the first and eighth HSE and LSE. During SETs 1 and 2, HSEs 1 and 8 there was a decrease in ionised Ca2+ and pH and a rise in lactate, intact PTH and P(i). LSEs 1 and 8 resulted in an increase in pH, whereas lactate, ionised Ca2+, total Ca, P(i) and intact PTH were not affected. No changes in calcium metabolism were detected during training. Results of this study suggest that intact PTH is a mediator in counter-regulation of exercise-induced hypocalcaemia.     

Effects of anaesthesia and manual restraint on the plasma concentrations of pituitary and adrenocortical hormones in ferrets

Two experiments were carried out to investigate the effect of sampling techniques on the plasma concentrations of pituitary and adrenocortical hormones in ferrets (Mustela putorius furo). In the first experiment blood was collected on two occasions from 29 ferrets which were either manually restrained or anaesthetised with isoflurane. In the second experiment eight intact ferrets were fitted with jugular catheters and blood was collected on four occasions, just before and as soon as possible after they had been manually restrained or anaesthetised with medetomidine or isoflurane; blood was also collected 10 and 30 minutes after the induction of anaesthesia. Medetomidine anaesthesia had no effect on the plasma concentrations of pituitary and adrenocortical hormones. Isoflurane anaesthesia resulted in a significant increase in the plasma concentration of alpha-melanocyte-stimulating hormone (alpha-MSH) directly after the induction of anaesthesia. Manual restraint resulted in a significant increase in the plasma concentrations of cortisol and adrenocorticotrophic hormone (ACTH) and a decrease in the plasma concentration of alpha-MSH.     

Acute effects of hypophysectomy and administration of pancreatic and thyroid hormones on circulating concentrations of somatomedin-C in young chickens: Relationship between growth hormone and somatomedin-C

The short-term control of plasma concentrations of somatomedin C (SmC) in young chicks was examined by either surgical removal of the pituitary gland or by the administration of hormones which affect plasma concentrations of growth hormone (GH). As expected, removal of the source of GH by hypophysectomy reduced plasma concentration of GH, these being suppressed by 95.7% within 1 hour. Hypophysectomy was rapidly followed by reductions in the plasma concentration of SmC. For instance, plasma concentrations of SmC were decreased to 53% of pretreatment one hour following hypophysectomy. This suggests both that SmC has a short half life and that the release of SmC into the circulation is tightly coupled to the presence of pituitary hormone(s), presumably including GH. Sham surgery also decreased plasma concentrations of GH but were without effect on plasma concentrations of SmC. The short term control of plasma concentrations of SmC was also examined by the acute administration of hormones, which affect GH secretion in vivo. Injections of thyroxine or triiodothyronine decreased the plasma concentration of GH but were without effect on the plasma concentration of SmC. On the other hand, the administration of either glucagon or insulin decreased the plasma concentration of both GH and SmC. The present data suggest that plasma concentrations of SmC do not simply reflect the GH status in young chickens.     

Changes in concentrations of plasma immunoreactive follicle-stimulating hormone, luteinizing hormone, estradiol-17beta, testosterone, progesterone, and inhibin in heifers from birth to puberty

This study was designed to clarify the characteristics of changes in plasma concentrations of reproductive hormones in heifers from birth to puberty. Weekly or daily hormonal changes were observed in 39 heifers. Daily changes in the concentration of follicle-stimulating hormone (FSH) demonstrated a consistent cycle of hormone changes over a 7- to 8-day period in heifers from approximately 10 days to 9 months old. Weekly changes in reproductive hormones showed that there were three brief periods in heifers between birth and puberty in which dramatic changes occur. The first period was the first week after birth, during which a reciprocal relationship between steroid hormones and gonadotropins was observed. At birth, the concentrations of steroid hormones were higher than those at any other age. These hormone levels rapidly decreased within the first week after birth. Gonadotropin levels, however, increased from birth to 1 week of age. The second period of major change was at approximately 4 weeks of age when there was an increase in the concentrations of luteinizing hormone (LH), estradiol-17beta, testosterone, and immunoreactive inhibin. The third period was the last 5 weeks before the first ovulation, when there was an increase in the concentrations of estradiol-17beta followed by an increase in (LH). These results suggest that regular hormone changes start from 10 days after birth and that the periods from birth to 4 weeks of age and the last 5 weeks before the first ovulation in heifers are important to the development of reproductive functions before puberty.     

Immune responses and plasma hormone concentrations in cold-exposed, xeranol-implanted calves

Hormonal involvement in the regulation of immune events was studied by exposing calves to cold air (-15 C) for 12 hours or by implanting animals with a growth promotant (xeranol) that is known to affect plasma hormone concentrations. Cold exposure significantly reduced serum IgM concentration by 23%, increased expression of tuberculin reactions to purified protein derivative by 60%, and augmented contact-sensitivity reactions to dinitrofluorobenzene by 31%. There was also a significant increase in plasma cortisol and insulin values and a reduction in growth hormone and prolactin values in cold-exposed calves. The cold-induced increase in contact reactions and plasma insulin was higher in xeranol-implanted calves, but the increase in plasma cortisol concentration caused by cold exposure tended to be reduced by the xeranol treatment. These data demonstrate that cold exposure alters immune reactions of calves and that these changes in immune events are associated with changes in a variety of plasma hormones. These results also indicate that it may be possible to augment immune reactions in vivo by appropriate hormonal modulation.     

Physiology of ghrelin and related peptides

Growth hormone (GH) released from pituitary under direct control of hypothalamic releasing (i.e., GHRH) and inhibiting (i.e., sst or SRIF) hormones is an anabolic hormone that regulates metabolism of proteins, fats, sugars and minerals in mammals. Cyril Bowers' discovery of GH-releasing peptide (GHRP-6) was followed by a search for synthetic peptide and nonpeptide GH-secretagogues (GHSs) that stimulate GH release, as well as a receptor(s) unique from GHRH receptor. GHRH and GHSs operate through distinct G protein-coupled receptors to release GH. Signal transduction pathways activated by GHS increase intracellular Ca2+ concentration in somatotrophs, whereas GHRH increases cAMP. Isolation and characterization of ghrelin, the natural ligand for GHS receptor, has opened a new era of understanding to physiology of anabolism, feeding behavior, and nutritional homeostasis for GH secretion and gastrointestinal motility through gut-brain interactions. Other peptide hormones (i.e., motilin, TRH, PACAP, GnRH, leptin, FMRF amide, galanin, NPY, NPW) from gut, brain and other tissues also play a role in modulating GH secretion in livestock and lower vertebrate species. Physiological processes, such as neurotransmission, and secretion of hormones or enzymes, require fusion of secretory vesicles at the cell plasma membrane and expulsion of vesicular contents. This process for GH release from porcine somatotrophs was revealed by atomic force microscopy (AFM), transmission electron microscopy (TEM) and immunohistochemical distribution of the cells in pituitary during stages of development.     

Annual Changes in Day-length,Temperature, and Circulating Reproductive Hormones in Thoroughbred Stallions and Geldings

Changes in follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, immunoreactive(ir)-inhibin, testosterone, estradiol-17β, and insulin-like growth factor (IGF)-I in Thoroughbred stallions along with changes in prolactin secretion in geldings were studied. The correlations of day-length with changes in the concentrations of these hormones were also studied. Five stallions and thirteen geldings were employed to draw blood samples in monthly basis and radioimmunoassay was performed to measure these hormones. All hormones showed a seasonal pattern, the levels being highest during the breeding season and lowest during the winter months. Most of the hormones were at their highest concentration during the month of April, the mid of spring in northern hemisphere. The concentration of circulating IGF-I also demonstrated seasonality, the peak lying on the month of April. The plasma concentration of prolactin also increased during the breeding season. This phenomenon was similar both in stallions and geldings although geldings had lower concentration than that of stallions. The changes in concentration of prolactin in stallions and geldings correlated more towards the day-length than towards the temperature. These results clearly indicate the seasonality of pituitary and gonadal hormones of Thoroughbred stallions, the activity being highest during the month of April and May of the breeding season.     

Effects of adrenergic agonists and insulin on porcine adipose tissue lipid metabolism in vitro

Because this laboratory has been able to demonstrate only a small and somewhat inconsistent stimulation of glucose metabolism by insulin in porcine adipose tissue in vitro, the tissue was preincubated with insulin to attempt to enhance the hormone effect. Preincubation with or without insulin did not increase insulin stimulation. Furthermore, insulin did not stimulate triacylglycerol biosynthesis. Adrenergic hormones stimulated lipolysis in porcine adipose tissue in vitro. Several analogs of norepinephrine incubated with porcine adipose tissue in vitro did not inhibit glucose incorporation into CO2 or total lipids, in contrast to inhibition observed in adipose tissue from other species. Isoproterenol inhibited glycerol-3-phosphate incorporation into lipids; the maximal inhibition was 50% for the initial stages of the pathway. Palmitate incorporation into lipids also was inhibited 50% by isoproterenol but this may have been an artifact. Preincubation of adipose tissue, with no exogenous hormone, might decrease the concentration of endogenous adrenergic hormones and thus make the tissue more responsive to exogenous adrenergic hormones. Preincubation of porcine adipose tissue did not consistently lower the basal lipolytic rate but enhanced the stimulated lipolytic rate; the mechanism is not known. These experiments provide no evidence that preincubation is beneficial to measurement of lipolysis or glucose metabolism in porcine adipose tissue in vitro.     

Effect of recombinant bovine tumor necrosis factor-α on hormone release in lactating cows

Tumor necrosis factor (TNF)‐α is a powerful macrophage cytokine released during infection, circulating in the blood to produce diverse effects in the organism. We examined the effect of recombinant bovine TNF‐α (rbTNF‐α) administration on hormone release in dairy cows during early lactation. Twelve non‐pregnant Holstein cows were treated subcutaneously with rbTNF‐α (2.5 µg/kg) or saline twice (at 11.00 and 23.00 hours). At 11.00 hours the next day, the cows were given growth hormone‐releasing hormone (GHRH, 0.25 µg/kg), thyrotrophin‐releasing hormone (TRH, 1.0 µg/kg), thyroid‐stimulating hormone (TSH, 10 µg/kg) or adrenocorticotropic hormone (500 µg/head) via the jugular vein. In the growth hormone‐releasing hormone challenge, the plasma growth hormone concentration was lower in the rbTNF‐α group than in the control (saline) group. The growth hormone and TSH responses to TRH were also smaller in the rbTNF‐α group than in the control. The plasma prolactin response to TRH was not affected by the rbTNF‐α treatment. In the TSH challenge, the rbTNF‐α‐treated cows had lower responses, as measured by plasma triiodothyronine and thyroxine, than the control cows. The rbTNF‐α treatment produced an increase in the basal plasma cortisol level, but the cortisol response to adrenocorticotropic hormone was the same level in both groups. The plasma concentrations of TNF‐α and interleukin‐1β in the cows were elevated by the rbTNF‐α treatment. The milk yield was reduced by the rbTNF‐α administration during 4 days. These data demonstrate that TNF‐α alters the secretion of pituitary and thyroid hormones in lactating cows. This effect may contribute to the suppression of the lactogenic function of the mammary gland observed in cases of coliform mastitis with high circulating TNF‐α levels.     

Hormonal responses to acute exercise, training and overtraining. A review with emphasis on the horse

Overtraining is an imbalance between training and recovery leading to symptoms associated with a neuroendocrine dysbalance called the overtraining syndrome, a disease characterized by behavioral, emotional and physical symptoms similar with depression. Although the prevalence of overtraining is high in human and equine athletes, at present no sensitive and specific test is available to prevent or diagnose overtraining. Nowadays, it is believed that combination of different (hormonal) parameters appear to be the best indicators of overtraining. Therefore, this review provides a summary of previous literature examining the response of the hypothalamic-pituitary-adrenal (HPA) axis and the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis to acute and chronic exercise as well as overtraining in humans and horses. The exercise induced hormonal responses seem to be equal for the equine as well as the human athlete, which makes comparisons possible. Repeated bouts of exercise are suggested to provide a way to detect subtle changes in hormonal responses in the individual athlete, which may make them an important tool in detecting early overtraining. This should be combined with corticotropin releasing hormone (CRH) stimulation tests and basal ACTH and GH pulsatility determination. Further research is needed to establish the correct training intensity and rest period for the exercise test in equines.     

Effects of thyroid hormones on serum and cutaneous fatty acid concentrations in dogs

The effects of thyroid hormones on the serum and cutaneous fatty acid concentration profiles of dogs were evaluated. Thyroidectomized dogs had significant (P less than 0.05) increases in serum oleic acid and linoleic acid concentrations, and decreases in concentration of dihomo-gamma-linolenic acid, arachidonic acid, and other elongation products of fatty acid metabolism. These changes were reversed in response to thyroid hormone replacement. Similar changes were found in cutaneous fatty acid concentration profiles. Thus, in dogs, thyroid hormones may be involved in the regulation of fatty acid delta-6-desaturase activity.     

The adverse effects of nicarbazin on reproductive activity in the hen.

The effects of the anticoccidial agent nicarbazin on reproductive activity in the female fowl have been studied. 2. The drug had no effect on the plasma concentration of luteinising hormone, but treated hens showed a reduced hypothalamic sensitivity to exogenous progesterone, whilst the capacity of the pituitary to respond to luteinising hormone releasing hormone was unimpaired. 3. It is suggested that nicarbazin not only prevents yolk deposition within the ovary but also adversely affects the stimulatory function of the hypothalamus, possibly through an unsuitable hormonal environment.     

Combined pituitary hormone deficiency in german shepherd dogs with dwarfism

In German shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.     

Pituitary dependent hyperadrenocorticism in a cat.

A cat that was suspected some insulin resistance was diagnosed as pituitary dependent hyperadrenocorticism from an adrenocorticotropic hormone (ACTH) stimulation test, dexamethasone suppression test and measure of endogenous plasma ACTH concentration. Histopathological examination revealed chromophobe adenoma in pituitary gland and hyperplasia in adrenal cortex.     

Role for des-acyl ghrelin in the responsiveness of plasma hormones and metabolites to ghrelin in Holstein steers

Gastric-derived peptide hormone ghrelin is known for its potent growth hormone (GH) stimulatory effects. The acyl-modification on N-terminal Ser(3) residue is reported to be important to stimulate the ghrelin receptor, GH secretagogue-receptor type1a (GHS-R1a). However, major portion of circulating ghrelin lacks in acylation, and some biological properties of des-acyl ghrelin have been reported in monogastric animals. In the present study, the responsiveness of plasma hormones and metabolites to ghrelin in steers was characterized, and role for des-acyl ghrelin in these changes was investigated. The repeated intravenous administrations of bovine ghrelin (1.0 microg/kg BW) every 2h for 8h to Holstein steers significantly increased the plasma acylated ghrelin, total ghrelin, GH, insulin and NEFA levels. The GH responses in peak values and area under the curves (AUCs) were attenuated by repeated injections of ghrelin, however, the responses of plasma total ghrelin were similar. Plasma insulin AUC decreased after fourth injection of ghrelin while plasma NEFA AUCs gradually increased by repeated injections of ghrelin. Pretreatment of des-acyl ghrelin (10.0 microg/kg BW) 5 min prior to the single injection of ghrelin (1.0 microg/kg BW) did not affect the ghrelin-induced hormonal changes. Moreover, the responses of plasma GH to bovine and porcine ghrelin, which differ in C-terminal amino acid residues, were similar in calves. These data show that (1) GH release was attenuated by repeated administration of ghrelin, (2) ghrelin regulates glucose and fatty acid metabolism probably via different pathway, and (3) des-acyl ghrelin is unlikely the antagonist for ghrelin to induce endocrine effects in Holstein steers.     

Apelin is involved in postprandial responses and stimulates secretion of arginine-vasopressin, adrenocorticotropic hormone, and growth hormone in the ruminant

Apelin and its mRNA are expressed in several tissues, including the supraoptic and paraventricular nuclei in the hypothalamus. Although apelin is reported to be involved in the regulation of fluid homeostasis, little is known about the postprandial dynamics of apelin in plasma and its regulatory effects on the anterior pituitary hormones of ruminants. Therefore, the aims of this study were to investigate the following: (1) changes in plasma apelin concentrations in response to food intake under conditions of hydration (free access to water) or dehydration (water restriction), and (2) the effects of intravenous administration of apelin on plasma concentrations of arginine-vasopressin (AVP), ACTH, GH, and insulin. In Experiment 1 with the use of goats, the postprandial plasma apelin concentration was significantly increased under the dehydration condition compared with the hydration condition, and this increase was accompanied by increased plasma concentrations of AVP and ACTH after 24 h of dehydration. In Experiment 2 with the use of sheep and hydration conditions, the intravenous administration of apelin ([Pyr(1)]-apelin-13; 0.5 mg/head) caused a tendency to increase or caused a significant increase in plasma concentrations of AVP, ACTH, GH, insulin, and glucose. On the basis of these findings, we concluded that apelin is involved in the feeding process, and it regulates endocrine functions in the anterior pituitary gland via AVP in ruminant animals.     

The drop in plasma thyrotropin concentrations in fasted chickens is caused by an action at the level of the hypothalamus: role of corticosterone

Fasting has severe effects on thyroid metabolism in the chicken: plasma thyroxine (T₄) concentrations increase, whereas 3′,5,3-triiodothyronine (T₃) concentrations decrease. In the present report we studied the effect of fasting at the level of: 1) the pituitary (plasma thyrotropin (TSH) concentrations; the sensitivity of thyrotrophs to corticotropin-releasing hormone (CRH) and TSH-releasing hormone (TRH)); and 2) the hypothalamus (TRH content). A regulatory role of corticosterone is discussed. One day of fasting resulted in a drop in plasma TSH concentrations. Fed and nonfed animals were treated with ovine CRH (oCRH) or TRH. The sensitivity of thyrotrophs to the respective hypothalamic hormones was increased when animals were subjected to a 1-d period of fasting. A 75% (TRH) and 50% (oCRH) increase in plasma TSH was recorded in fasted animals, whereas both secretagogues did not evoke any response in their fed counterparts. The drop in plasma TSH cannot, therefore, be attributed to a loss in sensitivity of thyrotrophs to hypothalamic stimulatory control. In an identical experiment, plasma TSH concentrations decreased, whereas hypothalamic TRH content was higher in fasted animals, suggesting a decreased hypothalamic TRH release toward the pituitary. In both fasting experiments, plasma corticosterone concentrations were increased after 1 d of fasting. Because an iv injection of corticosterone-elevated hypothalamic TRH contents and decreased plasma TSH concentrations, a corticosterone-induced TSH decrease during fasting is suggested through an action at the level of the hypothalamus.