Hypothalamic-pituitary Growth Research Articles

Diagnostic significance and considerations of growth hormone stimulation testing and insulin-like growth factor 1 in growth hormone deficiency

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.

Comparative survey of coordinated regulation of hypothalamic–pituitary–somatotropic axis in golden pompano (Trachinotus ovatus) and humpback grouper (Cromileptes altivelis)

Hypothalamic–Pituitary–Somatotropic (HPS) axis is the essential endocrine system playing important roles in animal growth. Here, the HPS axis were characterized in golden pompano (Trachinotus ovatus) and humpback grouper (Cromileptes altivelis), two marine cultured tropical teleosts representing fast and slow growth patterns, respectively. Through genomic and transcriptomic survey, 32 and 35 HPS genes were characterized in T. ovatus and C. altivelis. Functional domain and phylogeny revealed their conserved function among teleost lineages, with more ssts and igfbps identified and actively expressed in C. altivelis than in T. ovatus. The regulation of HPS genes responding to external stimuli revealed that T. ovatus HPS genes, including gh, igf1/2, igfbp1a/b, igfbp2b and igfbp5b, were differentially expressed under temperature or starvation challenges, while C. altivelis HPS genes were sensitive to salinity change with sst1.2, ghrhrb, igf1, igf2r, igfbp1a and igfbp5a regulated in brains. Strong interactive connectivity of igfbps was found in both T. ovatus and C. altivelis. Moreover, HPS genes evolved differently between T. ovatus and C. altivelis, and positively selected sites were detected in more C. altivelis HPS genes, like in functional domains of igf1ra and igf1rb. The igf1ra evolved faster than igf1rb in teleosts, which may contribute to their functional divergence. In conclusion, this study represented different regulatory and evolutionary patterns of HPS axis between T. ovatus and C. altivelis, which are vital in regulating their growth and will provide comprehensive insights into the cultivation of T. ovatus and C. altivelis in aquaculture.

Influence of Leptin on the Secretion of Growth Hormone in Ewes under Different Photoperiodic Conditions.

Leptin is an adipokine with a pleiotropic impact on many physiological processes, including hypothalamic-pituitary-somatotropic (HPS) axis activity, which plays a key role in regulating mammalian metabolism. Leptin insensitivity/resistance is a pathological condition in humans, but in seasonal animals, it is a physiological adaptation. Therefore, these animals represent a promising model for studying this phenomenon. This study aimed to determine the influence of leptin on the activity of the HPS axis. Two in vivo experiments performed during short- and long-day photoperiods were conducted on 12 ewes per experiment, and the ewes were divided randomly into 2 groups. The arcuate nucleus, paraventricular nucleus, anterior pituitary (AP) tissues, and blood were collected. The concentration of growth hormone (GH) was measured in the blood, and the relative expression of GHRH, SST, GHRHR, SSTR1, SSTR2, SSTR3, SSTR5, LEPR, and GH was measured in the collected brain structures. The study showed that the photoperiod, and therefore leptin sensitivity, plays an important role in regulating HPS axis activity in the seasonal ewe. However, leptin influences the release of GH in a season-dependent manner, and its effect seems to be targeted at the posttranscriptional stages of GH secretion.

562 Neuroendocrinology of human scalp hair follicles: Growth hormone-releasing hormone (GHRH) stimulates hair growth and controls a fully functional intrafollicular hypothalamic-pituitary-somatotropic (HPS) signaling axis

Human scalp hair follicles (HFs) are a major non-classical site of neurohormone production. While we had previously shown that growth hormone (GH), unexpectedly, inhibits female human scalp HFs growth ex vivo, it is unknown whether human HFs also produce key HPS axis neurohormones themselves, i.e. GH, its upstream regulator, GHRH, and/or the negative feedback control, somatostatin (SST), and whether GHRH modulates hair growth. To answer these questions, human scalp HFs were organ-cultured and stimulated with human GH (100 or 300ng/mL), GHRH (100 or 300ng/mL), or vehicle for mRNA or protein analysis of key HPS axis elements.

PMON17 Impaired cortisol regulation in Myotonic dystrophy

Abstract Introduction - Myotonic dystrophy (MD) is the most common cause of adult-onset muscular dystrophy. It has impaired HPA axis regulation with exaggerated ACTH response to CRH mediated stimuli and abnormal cortisol metabolism. We present a case of myotonic dystrophy in a male with elevated cortisol levels. Case report - 54-year-old male with a past medical history of type 1 myotonic dystrophy (MD1) presented for evaluation of hypogonadism with complaints of feeling fatigued, progressive weakness of muscles. During the workup, he was noted to have elevated cortisol levels 30.2 mcg/dL (6-18.4) with elevated ACTH 220 pg/mL (10-48). Other notable lab results included low total testosterone levels of 231, 185 with elevated LH of 17.3 m IU/ml (2-9) and FSH 37.7 m IU/ml (1-12). Prolactin levels were minimally elevated to 21.4 ng/mL (4-15.2). On further inquiry, the patient did not have headaches or vision changes. The patient did not report weight gain, easy bruising, change in facial appearance. Physical exam was significant for bilateral gynecomastia and small testes. No cushingoid facies, abdominal stria, proximal myopathy was noted. Given elevated ACTH and cortisol levels, further laboratory data showed a lack of suppression of cortisol levels with 1 mg dexamethasone - cortisol 2.9 micro g/dL (<1.8), elevated midnight salivary cortisol - 0.130, 0.102 ug/dl (0.010-0.090), and normal 24-hour urine cortisol levels -15 mcg/24 hours. Discussion – Even though Cushing's disease is one of the differential diagnoses for the above case, high cortisol levels have been reported in MD. Few mechanisms suggested causing this abnormality are increased ACTH responsiveness to CRH-mediated stimuli and abnormal cortisol metabolism. Patients with MD have high pro-inflammatory (IL-1 and TNF-a) markers, which mediate the increased ACTH responsiveness to CRH-mediated stimuli centrally by stimulating the HPA axis.1 In addition, IL-6 chronically stimulates steroidogenesis from the adrenal gland, whereas TNF-α inhibits ACTH-induced adrenal steroid synthesis and increases 11BHSD1 activity. Along with the impaired HP axis, abnormal metabolism of cortisol also contributes to elevated cortisol levels. Increased activity of 11 BHSD1 has been hypothesized to cause impaired clearance of cortisol.2 Impaired diurnal variation for cortisol is also seen in MD with elevated 24-hour cortisol levels. Elevated cortisol levels as in our case can be a diagnostic dilemma given impaired cortisol regulation as seen in MD. References Åsa Johansson et.al. Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 85, Issue 9, 1 September 2000, Pages 3169–76.Åsa Johansson et.al. Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 9, 1 September 2001, Pages 4276–83 Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

747 Human hair follicles functionally respond to growth hormone and growth hormone-releasing hormone, mimicking the central hypothalamic-pituitary-somatotropic axis

Human scalp hair follicles (HFs) are a major non-classical peripheral site of neurohormone production. However, it is unknown whether human scalp HFs also produce the key hypothalamic-pituitary-somatotropic (HPS) axis neurohormones, its main member growth hormone (GH), and its upstream hypothalamic regulator, GH-releasing hormone (GHRH). To answer this, we treated microdissected human scalp HFs with either human GH (100 or 300 ng/mL), or GHRH (100 or 300 ng/mL), for mRNA by qRT-PCR or protein analysis by quantitative immunohistomorphometry of key HPS axis elements.

Iturin A Rescued STb-R-Induced Pork Skeletal Muscle Growth Restriction through the Hypothalamic-Pituitary-mTORC1 Growth Axis.

Simple SummarySince antimicrobial peptides (AMPs) possess broad-spectrum antimicrobial activity and low drug resistance, their development as antibiotic alternatives are of interest. Previous studies reported that the performance of pigs was improved by AMPs through the protection of the intestine. Nevertheless, direct evidence linking AMPs and skeletal muscle growth is needed. In the current work, Iturin A as a novel antimicrobial peptide was selected to fight engineered STb-Rosetta Escherichia coli (STb-R) to measure pork skeletal muscle growth and further mechanisms. We found the restrictions of body weight gain and skeletal muscle growth caused by STb-R could be rescued after Iturin A gavage, and this was mediated by the hypothalamic-pituitary-Mtorc1 growth axis.The engineered STb-Rosetta Escherichia coli (STb-R) was designed to investigate the effects of Iturin A on the skeletal muscle growth of weaned piglets. A total of 28 piglets were randomly divided into 4 groups (7 piglets per group): the control group (100 mL PBS), the Iturin A group (100 mL 320 mg/kg body weight (BW) Iturin A), the STb-R group (100 mL 1 × 1010 CFU/mL STb-R), and the Iturin A + STb-R group (100 mL 320 mg/kg BW Iturin A + 1 × 1010 CFU/mL STb-R). Compared with the control, STb-R-reduced body weight gain were rescued by Iturin A. The semimembranosus muscle weight recovered to normal level in the Iturin A + STb-R group. The level of relevant genes of the growth axis were elevated by Iturin A, including GHRH in the hypothalamus, GHRHR and GH in the pituitary, and GHR, IGF-1 and IGF-1R in the semimembranosus muscle. Moreover, Iturin A increased the mean fiber area and the number of proliferating cells in the semimembranosus muscle, which were decreased by STb-R. Additionally, the mTORC1 pathway was reactivated by Iturin A to relieve the suppression of STb-R. Collectively, the hypothalamic-pituitary growth axis-mediated Iturin A reactivated the mTORC1 pathway to rescue STb-R-restricted pork skeletal muscle growth.

Growth, osmoregulatory and hypothalamic–pituitary–somatotropic (HPS) axis response of the juvenile largemouth bass (Micropterus salmoides), reared under different salinities

A 40 day experiment was conducted to investigate the effects of different salinities (0, 5 and 10 ppt) on the growth, osmoregulatory and hypothalamic–pituitary–somatotropic (HPS) axis response of juvenile largemouth bass (Micropterus salmoides). At the same time, two extra groups salinities (8 and 9 ppt) were used to explore the threshold of osmoregulation in M. salmoides to salinity stress. The survival were 94.45 %, 98.15 % and 32.00 % in 0, 5, 10 ppt, respectively. According the final body weight, specific growth rate (SGR), feed conversion ratio (FCR), condition factor (K) and chemical composition of muscle, largemouth bass should not be cultured at or above 10 ppt and 5 ppt is better than 0 ppt. The results found that the content of serum prolactin (PRL) and cortisol (COR) were no significant differences between groups of the 0, 5, 8, 9 and 10 ppt. Compared with the control group (0 ppt), the serum thyroxine (T4) content of 8 and 9 ppt groups decreased significantly and the serum triiodothyronine (T3) content all decreased significantly. Serum osmolality increased with increasing salinity. Na+-K+-ATP (NKA) and Ca2+-Mg2+-ATP (CMA) activities in the gills of largemouth bass at 0, 5, 8, 9 and 10 ppt showed tendency of ascend at first and descend at last, among which the activities in 10 ppt were significantly lowest. Gene expression of hepatic growth hormone (GH) at 10 ppt was highest. Meanwhile, insulin-like growth factor-I (IGF-I) expression at salinities of 8, 9 and 10 ppt were significantly higher than those at 0 and 5 ppt. Taken together, the findings of this study provide guidance for the practical rearing of largemouth bass in saline waters and contribute to research on stress physiology.

Markers of Genetic Variation in Blue Gourami (Trichogaster trichopterus) as a Model for Labyrinth Fish.

Simple SummaryThis review is a summary of recent studies of genes, many of them involved in growth and reproduction, which can be used for distinguishing between species of the Anabantoidei suborder of fish, focusing on the Blue Gourami as a model species. This is important in both basic science and aquaculture applications. Markers of genetic variation between species are important for both applied and basic research. Here, various genes of the blue gourami (Trichogaster trichopterus, suborder Anabantoidei, a model labyrinth fish), many of them involved in growth and reproduction, are reviewed as markers of genetic variation. The genes encoding the following hormones are described: kisspeptins 1 and 2, gonadotropin-releasing hormones 1, 2, and 3, growth hormone, somatolactin, prolactin, follicle- stimulating hormone and luteinizing hormone, as well as mitochondrial genes encoding cytochrome b and 12S rRNA. Genetic markers in blue gourami, representing the suborder Anabantoidei, differ from those in other bony fishes. The sequence of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene of blue gourami is often used to study the Anabantoidei suborder. Among the genes involved in controlling growth and reproduction, the most suitable genetic markers for distinguishing between species of the Anabantoidei have functions in the hypothalamic–pituitary–somatotropic axis: pituitary adenylate cyclase-activating polypeptide and growth hormone, and the 12S rRNA gene.

Somatotropic-Testicular Axis: A crosstalk between GH/IGF-I and gonadal hormones during development, transition, and adult age.

The hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-somatotropic (HPS) axes are strongly interconnected. Interactions between these axes are complex and poorly understood. These interactions are characterized by redundancies in reciprocal influences at each level of regulation and the combination of endocrine and paracrine effects that change during development. To comprehensively review the crosstalk between the HPG and HPS axes and related pathological and clinical aspects during various life stages of male subjects. A thorough search of publications available in PubMed was performed using proper keywords. Molecular studies confirmed the expressions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) receptors on the HPG axis and reproductive organs, indicating a possible interaction between HPS and HPG axes at various levels. Insulin growth factors participate in sexual differentiation during fetal development, indicating that normal HPS axis activity is required for proper testicular development. IGF-I contributes to correct testicular position during minipuberty, determines linear growth during childhood, and promotes puberty onset and pace through gonadotropin-releasing hormone activation. IGF-I levels are high during transition age, even when linear growth is almost complete, suggesting its role in reproductive tract maturation. Patients with GH deficiency (GHD) and insensitivity (GHI) exhibit delayed puberty and impaired genital development; replacement therapy in such patients induces proper pubertal development. In adults, few studies have suggested that lower IGF-I levels are associated with impaired sperm parameters. The role of GH-IGF-I in testicular development remains largely unexplored. However, it is important to evaluate gonadic development in children with GHD. Additionally, HPS axis function should be evaluated in children with urogenital malformation or gonadal development alterations. Correct diagnosis and prompt therapeutic intervention are needed for healthy puberty, attainment of complete gonadal development during transition age, and fertility potential in adulthood.

SUN-031 Megestrol Acetate for Bodybuilding Resulting in Abrupt Hypothalamic-Pituitary Dysfunction

Introduction: Megestrol acetate (MA) is a synthetic progestin often used for appetite stimulation and weight gain in patients with cachexia related to AIDS, cancer or terminal illness. MA is frequently implicated in development of both glucocorticoid excess and adrenal insufficiency (AI) in a somewhat unpredictable manner. Less commonly reported adverse effects of MA include dysfunction of the hypothalamic pituitary axis. Few cases in literature exist regarding the use of MA in young, healthy patients and the potential clinical severity of pituitary dysfunction in this population. Case: A 24-year-old male was previously healthy but frustrated by an inability to gain muscle mass. Evaluation one-year prior was unrevealing and included a total testosterone of 1100ng/dL (264-916ng/dL). In the interim, he was prescribed MA 625/5mg for 2 months with rapid development of abdominal adiposity, depressed mood, low libido and erectile dysfunction. Repeat evaluation revealed a precipitous drop in total testosterone to 66 ng/dL at which point he self-discontinued MA. He then began to experience palpitations, sweats, poor concentration, and undesirable weight loss along with worsening symptoms of sexual and erectile dysfunction.Three months after MA discontinuation, he appeared well with physical examination and vital signs within normal limits. Surprisingly, repeat studies revealed total testosterone <3, free testosterone <0.2 (9.3 -26.5 pg/mL), LH 1.3 (1.7-8.6 mIU/mL), FSH 2.2 (1.5-12.3 mIU/mL), Prolactin 33.4 (4.0-15.2 ng/mL) as well as 8AM cortisol 2.2 ug/dL and ACTH 22.7 pg/mL. A basic metabolic panel, thyroid function studies and pituitary MRI were unremarkable. The patient was empirically placed on prednisone 5mg daily pending ACTH stimulation testing for HPA axis reassessment. Topical testosterone replacement therapy was initiated due to intolerance of hypogonadal symptoms. Discussion: MA, by virtue of affinity for glucocorticoid receptors, has the potential to cause hyperglycemia and Cushing’s syndrome. Secondary AI often results from withdrawal of MA however central AI can also occur with active administration by unclear mechanisms. Hypogonadism and hyperprolactinemia are additional under-reported adverse effects of MA with symptoms often masked by AI or elements of chronic illness. In study of men age 60-85 year on MA, a mean percentage change of ACTH -89.5%, LH -49%, TSH -14.7% and Prolactin +150% were seen from baseline after 12 weeks of therapy as was decreased cortisol. Limited data exists in young patients such as ours given limited indications for the agent’s use. Importantly, MA should be prescribed with understanding that weight gain is predominantly adipose rather than muscle mass and that its safety is limited by potential HP axis dysfunction, namely adrenal and gonadal deficiencies.

Factors influencing GH and IGF‐I gene expression on growth in teleost fish: how can aquaculture industry benefit?

AbstractGrowth is a polygenic and environmentally controlled trait with the most influential genes being those of growth hormone (GH) and insulin‐like growth factor‐I (IGF‐I), as they consist the core of the hypothalamic–pituitary–somatotropic (HPS) axis. As a result, the influence of environmental and dietary conditions on GH and IGF‐I gene expression has a great potential in planning to optimize fish health and production, as growth rate of fish is a key factor in aquaculture. In this review, we provide a molecular and physiological overview of GH and IGF‐I gene expression as well as all the participating factors regulating GH/IGF‐I axis in growth. We further discuss the genetic, dietary and environmental factors affecting growth rate. More importantly, how external factors in combination with diet such as temperature, photoperiod, salinity, pollutants and stocking density affect GH and IGF‐I expression and growth rate. In addition, there is evidence that photoperiod effect varies among species by altering the seasonal cycle of GH and IGF‐I gene expression and biological cycle of fish. Pollution has also a variable effect on GH, IGF‐I and fish growth rate, depending on the pollutant, species and sex. Finally, increased stocking density influences the HPS axis and growth, dependent on species, temperature and the stage of growth. Notably, interactions among these factors were observed by the reported importance, primarily feeding‐related stress one of the most important factors, while environmental would add or subtract on each other’s optimal or suboptimal conditions in a hierarchy of significance, as further discussed.

NCMP-07. SECONDARY ADRENAL INSUFFICIENCY IN ADULT PATIENTS WITH GLIOMA: A CASE SERIES

Abstract Glucocorticoids (GC) are a mainstay in the treatment of gliomas to reduce cerebral edema and improving symptoms related to swelling. Prolonged GC use can lead to adrenal insufficiency (AI) due to the suppression of the hypothalamic-pituitary-adrenal axis. AI is challenging to diagnose as the tumor itself or the chemotherapy are blamed for the symptoms. This study aims to evaluate the risk factors predisposing patients with gliomas to develop AI during their treatment course. METHODS This is a retrospective case review. Charts in the neuro-oncology clinic from July 2018 to March 2018 were reviewed. Inclusion criteria include &gt; 18 y/o, diagnosis of glioma WHO Grade II to IV, and diagnosis of secondary AI. Demographic profile, tumor characteristics, radiation dose, exposure or proximity to HPA, current treatment, and dexamethasone dose and duration of treatment were tabulated and compared. RESULTS Nine of ten patients were started on high dose of dexamethasone (&gt; 8mg daily), and only one was started on a lower dose (&lt; 4mg daily). Majority of the patients (50%) were on dexamethasone for less than a year (4–8 months), and a significant portion (40%) of the patients remained on dexamethasone for &gt; 2 years, with one patient on steroids for 64 months. The minimum dose of dexamethasone needed to prevent symptoms ranged from 0.5mg to 2mg daily. Most received 60Gy of radiation, two received 59.4 Gy, and one received 54 Gy. Six patients had radiation exposure to the HP axis, while four didn’t. CONCLUSION Secondary adrenal insufficiency results from prolonged glucocorticoid use in patients with glioma. Dose and duration of GC are risk factors to its development. Radiation to the HPA axis may be a contributing factor to the development of AI in patients with glioma, although it can also be seen in patients with radiation distant from the HPA.

Modelling the dynamics of temperature field morphology of a heat pipe with a case defect

As part of a computer experiment with the use of the finite element method, a method was developed for analyzing the morphology of the non-stationary temperature field of a heat pipe which has a localized structure defect in its case. It is shown that within the model of a steady start of HP (τ = 0 ÷ 120 s.) and maximum temperatures of PHFS TPHFS = 350 ÷ 400 K, the presence of a defect causes the variability of the shape of isotherms over time and the nature of the temperature distribution along the HP axis. In this case, the distance from the center of the HP to the front of the isothermal line uniquely determines changes in the morphology of the temperature field.

Hypothalamic-pituitary axis irradiation dose thresholds for the development of hypopituitarism in adult-onset gliomas.

Childhood brain tumour survivors who receive cranial radiotherapy undergo regular surveillance for the development ofhypothalamic-pituitary (HP) axis dysfunction. Much less attention has been given to radiation-induced hypopituitarism in patients with malignant brain tumours of adult onset. Retrospective cohort study. We assessed the effects of cranial radiotherapy (cXRT) on pituitary function in 58 adults (32 male) with gliomas distant to the HP axis. The XRT dose exposure at the HP axis was correlated with individual axis dysfunction to establish dose thresholds. Mean age at cXRT was 41.2±10.9years and duration of endocrine follow-up 8.2±5.2years. Mean XRT dose to the HP axis was 35.9±15.5Gy. Overall prevalence of radiation-induced hypopituitarism was 84.5%. GH, LH/FSH, ACTH and TSH deficiency were present in 82.8%, 20.7%, 19% and 6.9% of patients, respectively. Hyperprolactinaemia was noted in 10.3% (n=6) and was persistent in one case. GH deficiency and "any degree of hypopituitarism" positively correlated with the radiotherapy dose to the hypothalamic-pituitary axis. HP axis XRT dose thresholds for the development of GHD, LH/FSH, ACTH and TSH deficiency were established at 10, 30, 32 and 40.8Gy, respectively. A gradual increase in the prevalence of all anterior pituitary hormone deficits was observed throughout the follow-up period. Hypopituitarism post-cXRT in adults with gliomas is a frequent, progressive and dose-dependent phenomenon. Dose thresholds suggest long-term endocrine surveillance is important where the HP axis XRT dose is higher than 30Gy. Identification of deficits to allow early and appropriate hormone replacement therapy is important to improve well-being in these individuals with limited prognosis.

Exploring the mechanistic link between corticosterone and insulin-like growth factor-1 in a wild passerine bird

BackgroundPhysiological regulators of life history trade-offs need to be responsive to sudden changes of resource availability. When homeostasis is challenged by unpredictable stressors, vertebrates respond through a set of physiological reactions, which can promote organismal survival. Glucocorticoids have been traditionally recognized as one of the main regulators of the physiological stress response, but the role of an evolutionarily more conserved pathway, the hypothalamic-pituitary-somatotropic (HPS) axis producing insulin-like growth factor-1 (IGF-1) has received much less attention. Although IGF-1 is known to affect several life history traits, little is known about its role in the physiological stress response and it has never been studied directly in adult wild animals.MethodsIn this study, we combined field observations with a controlled experiment to investigate how circulating levels of IGF-1 change in response to stress and whether this change is due to concomitant change in glucocorticoids in a free-living songbird, the bearded reedling Panurus biarmicus. We used a standard capture-restraint protocol in field observation, in which we took first and second (stress induced: 15 minutes later) samples. In a follow-up experiment, we used a minimally invasive oral corticosterone manipulation.ResultsWe showed that corticosterone levels significantly increased while IGF-1 levels significantly decreased during capture and handling stress. However, change in corticosterone levels were not related to change in IGF-1 levels. We found that experimentally elevated corticosterone levels did not affect IGF-1 levels.DiscussionOur results are the first to highlight that circulating IGF-1 levels are responsive to stress independently from glucocorticoids and suggest that the HPS axis is an autonomous physiological pathway that may play an important role as regulator of life-history decisions.

Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal.

Siberian hamsters (Phodopus sungorus) show spontaneous daily torpor only after ∼2 mo in winter-like short photoperiods (SP). Although some SP-induced hormonal changes have been demonstrated to be necessary for the occurrence of seasonal torpor, the whole set of preconditions is still unknown. Recent findings provide evidence that the hypothalamic pituitary growth axis is involved in endocrine responses to SP exposure in the photoperiodic hamsters. To examine whether suppression of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion affects the incidence of daily torpor, we used two somatostatin receptor agonists, pasireotide (SOM230) and octreotide, with different affinity profiles for receptor subtypes. Pasireotide strikingly increased the torpor frequency in male hamsters compared with sham-treated controls, and torpor duration was often increased, which in some cases exceeded 12 h. In contrast, administration of octreotide reduced the body weight of SP hamsters but had only a marginal effect on torpor frequency in males and no effect in females. Together with measured concentrations of circulating IGF-1, the present results strongly suggest that reduced activity of the GH/IGF-1 axis is not critical for stimulation of torpor expression but activation of specific somatostatin receptors is critical. This putative role for certain somatostatin receptor subtypes in torpor induction provides a promising new approach to unravel the endocrine mechanisms of torpor regulation.

Stress Response and Endocrine Deregulation during Critical Illness

The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that arrive through distinct pathways. Activation of the stress system leads to behavioral and physical changes that are remarkably consistent in their qualitative presentation. The stress response is mediated largely by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, which includes the sympathetic nervous system and the adrenal medulla. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The time-limited nature of this process renders its accompanying antigrowth, antireproductive, catabolic, and immunosuppressive effects temporarily beneficial and/or of no adverse consequence to the individual. However, chronic activation of the stress system as occurs in critically ill patients may lead to a number of disorders, including stress hyperglycemia, dysfunction of the HPA and hypothalamic-pituitary-thyroid (HPT) axes, and hypothalamic-pituitary growth hormone (GH) dysfunction. These disorders are reviewed in this chapter. Diagnosis of adrenal insufficiency/critical illness–related corticosteroid insufficiency and who to treat with steroids are also covered in depth. The author emphasizes the controversial management of these deregulated hormonal axes with only limited data supporting an improvement in outcome with hormonal replacement therapy. This review contains 3 Figures, 1 Table, 39 References, 5 Board-Styled MCQs, and a Teaching Slide Set for teaching and reference purposes.

Stress Response and Endocrine Deregulation during Critical Illness

The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that arrive through distinct pathways. Activation of the stress system leads to behavioral and physical changes that are remarkably consistent in their qualitative presentation. The stress response is mediated largely by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, which includes the sympathetic nervous system and the adrenal medulla. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The time-limited nature of this process renders its accompanying antigrowth, antireproductive, catabolic, and immunosuppressive effects temporarily beneficial and/or of no adverse consequence to the individual. However, chronic activation of the stress system as occurs in critically ill patients may lead to a number of disorders, including stress hyperglycemia, dysfunction of the HPA and hypothalamic-pituitary-thyroid (HPT) axes, and hypothalamic-pituitary growth hormone (GH) dysfunction. These disorders are reviewed in this chapter. Diagnosis of adrenal insufficiency/critical illness–related corticosteroid insufficiency and who to treat with steroids are also covered in depth. The author emphasizes the controversial management of these deregulated hormonal axes with only limited data supporting an improvement in outcome with hormonal replacement therapy. This review contains 3 Figures, 1 Table, 39 References, 5 Board-Styled MCQs, and a Teaching Slide Set for teaching and reference purposes.

Stress Response and Endocrine Deregulation during Critical Illness

The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that arrive through distinct pathways. Activation of the stress system leads to behavioral and physical changes that are remarkably consistent in their qualitative presentation. The stress response is mediated largely by the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, which includes the sympathetic nervous system and the adrenal medulla. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The time-limited nature of this process renders its accompanying antigrowth, antireproductive, catabolic, and immunosuppressive effects temporarily beneficial and/or of no adverse consequence to the individual. However, chronic activation of the stress system as occurs in critically ill patients may lead to a number of disorders, including stress hyperglycemia, dysfunction of the HPA and hypothalamic-pituitary-thyroid (HPT) axes, and hypothalamic-pituitary growth hormone (GH) dysfunction. These disorders are reviewed in this chapter. Diagnosis of adrenal insufficiency/critical illness–related corticosteroid insufficiency and who to treat with steroids are also covered in depth. The author emphasizes the controversial management of these deregulated hormonal axes with only limited data supporting an improvement in outcome with hormonal replacement therapy. This review contains 3 Figures, 1 Table, 39 References, 5 Board-Styled MCQs, and a Teaching Slide Set for teaching and reference purposes.