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Neuroscience Research May 2017Sleep is one of the most important physiological functions in mammals. It is regulated by not only homeostatic regulation but also circadian clock. Several... (Review)
Review
Sleep is one of the most important physiological functions in mammals. It is regulated by not only homeostatic regulation but also circadian clock. Several neuropeptide-producing neurons located in the hypothalamus are implicated in the regulation of sleep/wakefulness. Among them, orexin/hypocretin-producing neurons (orexin neurons) are a crucial component for maintenance of wakefulness, because lack of orexin function results in narcolepsy, which is a sleep disorder. Recent findings have identified substances that excite or inhibit neural activity of orexin neurons. Furthermore neural projections of the neurons which release these substances have been revealed. In addition to orexin, melanin concentrating hormone (MCH)-producing neurons in the lateral hypothalamic area (LHA) are also implicated in the regulation of sleep/wakefulness. MCH neurons are active during sleep but become silent during wakefulness. Recently developed innovative methods including optogenetics and pharmacogenetics have provided substantial insights into the regulation of sleep/wakefulness. In vivo optical recordings and retrograde and anterograde tracing methods will allow us to understand additional details regarding important interactions between these two types of neurons in the LHA and other neurons in the brain. Finally we discuss the circadian clock and sleep/wake cycle. Understanding of the neural networks and its circadian modulation of sleep/wake cycles remain to be investigated.
Topics: Animals; Humans; Hypothalamic Hormones; Hypothalamus; Melanins; Orexins; Pituitary Hormones; Sleep; Wakefulness
PubMed: 28526553
DOI: 10.1016/j.neures.2017.03.013 -
Communications Biology Aug 2021The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we...
The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we found in the teleost medaka that two neuropeptides belonging to the secretin family, pituitary adenylate cyclase-activating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), exhibit opposite patterns of sexually dimorphic expression in the same population of POA neurons that project to the anterior pituitary: Pacap is male-biased, whereas Vip is female-biased. Estrogen secreted by the ovary in adulthood was found to attenuate Pacap expression and, conversely, stimulate Vip expression in the female POA, thereby establishing and maintaining their opposite sexual dimorphism. Pituitary organ culture experiments demonstrated that both Pacap and Vip can markedly alter the expression of various anterior pituitary hormones. Collectively, these findings show that males and females use alternative preoptic neuropeptides to regulate anterior pituitary hormones as a result of their different estrogen milieu.
Topics: Animals; Estrogens; Female; Fish Proteins; Male; Neuropeptides; Oryzias; Pituitary Hormones; Preoptic Area; Sex Characteristics
PubMed: 34373576
DOI: 10.1038/s42003-021-02476-5 -
Neuro-oncology Apr 2024Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess...
BACKGROUND
Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency.
METHODS
Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves.
RESULTS
A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years.
CONCLUSIONS
SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.
Topics: Humans; Male; Middle Aged; Follow-Up Studies; Hypopituitarism; Pituitary Hormones; Pituitary Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome; Female
PubMed: 38095431
DOI: 10.1093/neuonc/noad215 -
Nature Reviews. Endocrinology Dec 2021Melanin-concentrating hormone (MCH) is a small cyclic peptide expressed in all mammals, mainly in the hypothalamus. MCH acts as a robust integrator of several... (Review)
Review
Melanin-concentrating hormone (MCH) is a small cyclic peptide expressed in all mammals, mainly in the hypothalamus. MCH acts as a robust integrator of several physiological functions and has crucial roles in the regulation of sleep-wake rhythms, feeding behaviour and metabolism. MCH signalling has a very broad endocrine context and is involved in physiological functions and emotional states associated with metabolism, such as reproduction, anxiety, depression, sleep and circadian rhythms. MCH mediates its functions through two receptors (MCHR1 and MCHR2), of which only MCHR1 is common to all mammals. Owing to the wide variety of MCH downstream signalling pathways, MCHR1 agonists and antagonists have great potential as tools for the directed management of energy balance disorders and associated metabolic complications, and translational strategies using these compounds hold promise for the development of novel treatments for obesity. This Review provides an overview of the numerous roles of MCH in energy and glucose homeostasis, as well as in regulation of the mesolimbic dopaminergic circuits that encode the hedonic component of food intake.
Topics: Animals; Homeostasis; Humans; Hypothalamic Hormones; Mammals; Melanins; Pituitary Hormones
PubMed: 34608277
DOI: 10.1038/s41574-021-00559-1 -
Acta Neurochirurgica Oct 2020Pre-/postoperative pituitary endocrine deficiencies in patients with sellar/parasellar non-adenomatous lesions are poorly described and studies have not considered the...
BACKGROUND
Pre-/postoperative pituitary endocrine deficiencies in patients with sellar/parasellar non-adenomatous lesions are poorly described and studies have not considered the effect of sellar invasion on endocrine outcome. The aim of this study was to relate the need for pituitary hormone replacement pre-/postoperatively, with sellar invasion, in non-adenomatous sellar/parasellar lesions.
METHODS
Single-centre review of adults with histologically confirmed non-adenomatous sellar/parasellar lesion and follow-up ≥ 3 months or until postop radiotherapy. Pituitary dysfunction was defined by hormone replacement. The sellar encroachment score (0-6) was calculated as the sum of the thirds of radiological encroachment into the sellar region in the coronal and sagittal planes. Multivariate analysis with binary logistic regression was used to determine factors associated with pituitary hormone replacement.
RESULTS
One hundred and seventeen patients were included with a median age of 49 years (range 16-84 years) and median follow-up of 13 months. Surgery was trans-sphenoidal (53%), trans-cranial (36%) or a combination (11%). The commonest histology types were meningioma (n = 33, 28%) and craniopharyngioma (n = 20, 17%). The median sellar encroachment score was 6 (range 0-6). Most (n = 86, 74%) did not require pituitary hormone replacement preoperatively. The need for pituitary hormones increased after surgery in 41 (35%) patients. In multivariate analysis, the sellar encroachment score was the only factor predictive of pre- (OR = 2.6, 95% CI = 1.2-5.5; p = 0.01) and postoperative risk of new pituitary hormone replacement (OR = 4.1, 95% CI = 1.7-10.1, p = 0.002).
CONCLUSION
A significant proportion of these patients present with need for pituitary hormone replacement that may worsen postoperatively. The degree of sellar encroachment is predictive of pituitary hormone replacement status pre-/postoperatively.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Craniopharyngioma; Female; Hormone Replacement Therapy; Humans; Magnetic Resonance Imaging; Male; Meningioma; Middle Aged; Pituitary Hormones; Pituitary Neoplasms; Postoperative Care; Prospective Studies; Sella Turcica; Skull; Sphenoid Bone; Young Adult
PubMed: 32506330
DOI: 10.1007/s00701-020-04440-4 -
Deutsche Medizinische Wochenschrift... Mar 2023Pituitary insufficiency is a partial or complete failure of secretion of one or more hormones from the pituitary gland. The pituitary gland is located in the hypophysial...
Pituitary insufficiency is a partial or complete failure of secretion of one or more hormones from the pituitary gland. The pituitary gland is located in the hypophysial fossa of the sella turcica of the os sphenoidale and produces ACTH, LH, FSH, GH, TSH, and prolactin. Pituitary insufficiency can be caused by acute damage, such as secondary to traumatic brain injury. It can also be a result of chronic alterations, such as increasing tumor expansion.Pituitary insufficiency often presents with nonspecific symptoms (e.g. fatigue, listlessness, decreased performance, sleep disturbances, weight change) that leads to a challenging and sometimes delayed diagnosis. The symptoms correspond to the failure of the corresponding endorgans. Occasionally, symptoms such as a loss of libido, secondary amenorrhea or nausea in stressful situations are diagnostically indicative.Further clarification includes a clinical examination with endocrinological testing of the pituitary function. Alteration of pituitary hormone secretion can also occur physiologically as in pregnancy, depression or obesity. Substitution therapy of the failed corticotropic, thyrotropic and gonadotropic axis is corresponding to the therapy of a primary endorgan insufficiency. Adequate diagnosis and treatment of pituitary insufficiency is important, as this may prevent life-threatening crises such as an adrenal crisis.
Topics: Female; Pregnancy; Humans; Prolactin; Pituitary Gland; Hypopituitarism; Hormones
PubMed: 36940689
DOI: 10.1055/a-1853-5881 -
Clinical Endocrinology Sep 2017Patients with microprolactinoma and idiopathic hyperprolactinaemia are not generally considered to be at risk of hypopituitarism and are therefore not routinely screened...
INTRODUCTION
Patients with microprolactinoma and idiopathic hyperprolactinaemia are not generally considered to be at risk of hypopituitarism and are therefore not routinely screened for this abnormality. In our clinical practice, we have observed a number of patients with nonmacroadenomatous hyperprolactinaemia to have anterior pituitary hormone deficits.
AIMS
We aimed to establish the frequency and clinical significance of anterior pituitary hormone deficiencies, comparing patients with radiologically proven microprolactinomas and patients with idiopathic hyperprolactinaemia.
STUDY DESIGN
We retrospectively examined the casenotes of 206 patients with hyperprolactinaemia from our centre. Patients who did not fit the profile of surgically naïve microprolactinoma or idiopathic hyperprolactinaemia or who had incomplete data were excluded, resulting in a study group of 56 patients.
RESULTS
A total of 35 patients with MRI evidence of microprolactinoma were identified, three (8.57%) of whom had one or more anterior pituitary hormone deficiencies. A total of 21 patients with MRI-negative idiopathic hyperprolactinaemia were identified, nine (42%) of whom had one or more anterior pituitary hormone deficiencies (P<.01). Only one patient in the MRI-positive group had deficiency that required hormone replacement, in contrast six patients in the MRI-negative group had deficiencies that were of clinical significance and which required hormone replacement.
SUMMARY
This study shows a clinically significant incidence of anterior pituitary hormone deficiency in patients with idiopathic hyperprolactinaemia. The authors recommend that dynamic pituitary assessment should be considered routinely in this patient group. A prospective study would be required to assess the underlying cause for these abnormalities, as they suggest a nontumour pan-pituitary process.
Topics: Female; Hormone Replacement Therapy; Humans; Hyperprolactinemia; Hypopituitarism; Incidence; Magnetic Resonance Imaging; Male; Pituitary Hormones, Anterior; Prolactinoma; Retrospective Studies
PubMed: 28425105
DOI: 10.1111/cen.13355 -
The Journal of Physiology Nov 2016The hypothalamus is among the most phylogenetically conserved regions in the vertebrate brain, reflecting its critical role in maintaining physiological and behavioural... (Review)
Review
The hypothalamus is among the most phylogenetically conserved regions in the vertebrate brain, reflecting its critical role in maintaining physiological and behavioural homeostasis. By integrating signals arising from both the brain and periphery, it governs a litany of behaviourally important functions essential for survival. In particular, the lateral hypothalamic area (LHA) is central to the orchestration of sleep-wake states, feeding, energy balance and motivated behaviour. Underlying these diverse functions is a heterogeneous assembly of cell populations typically defined by neurochemical markers, such as the well-described neuropeptides hypocretin/orexin and melanin-concentrating hormone. However, anatomical and functional evidence suggests a rich diversity of other cell populations with complex neurochemical profiles that include neuropeptides, receptors and components of fast neurotransmission. Collectively, the LHA acts as a hub for the integration of diverse central and peripheral signals and, through complex local and long-range output circuits, coordinates adaptive behavioural responses to the environment. Despite tremendous progress in our understanding of the LHA, defining the identity of functionally discrete LHA cell types, and their roles in driving complex behaviour, remain significant challenges in the field. In this review, we discuss advances in our understanding of the neurochemical and cellular heterogeneity of LHA neurons and the recent application of powerful new techniques, such as opto- and chemogenetics, in defining the role of LHA circuits in feeding, reward, arousal and stress. From pioneering work to recent developments, we review how the interrogation of LHA cells and circuits is contributing to a mechanistic understanding of how the LHA coordinates complex behaviour.
Topics: Animals; Brain; Humans; Hypothalamic Area, Lateral; Hypothalamic Hormones; Melanins; Neurons; Neuropeptides; Pituitary Hormones
PubMed: 27302606
DOI: 10.1113/JP271946 -
Current Treatment Options in Oncology Sep 2016Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors.... (Review)
Review
Survival rates of childhood cancer have improved markedly, and today more than 80 % of those diagnosed with a pediatric malignancy will become 5-year survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at particularly high risk for long-term morbidity, such as endocrine insufficiencies, metabolic complications, and cardiovascular morbidity. Deficiencies of one or more anterior pituitary hormones have been described following therapeutic CRT for primary brain tumors, nasopharyngeal tumors, and following prophylactic CRT for childhood acute lymphoblastic leukemia (ALL). Studies have consistently shown a strong correlation between the total radiation dose and the development of pituitary deficits. Further, age at treatment and also time since treatment has strong implications on pituitary hormone deficiencies. There is evidence that the hypothalamus is more radiosensitive than the pituitary and is damaged by lower doses of CRT. With doses of CRT <50 Gy, the primary site of radiation damage is the hypothalamus and this usually causes isolated GH deficiency (GHD). Higher doses (>50 Gy) may produce direct anterior pituitary damage, which contributes to multiple pituitary deficiencies. The large group of ALL survivors treated with CRT in the 70-80-ties has now reached adulthood, and these survivors were treated mainly with 24 Gy, and the vast majority of these patients suffer from GHD. Further, after long-term follow-up, insufficiencies in prolactin (PRL) and thyroid stimulating hormone (TSH) have also been reported and a proportion of these patients were also adrenocoticotrophic hormone (ACTH) deficient. CRT to the hypothalamus causes neuroendocrine dysfunction, which means that the choice of GH test is crucial for the diagnosis of GHD.
Topics: Adrenocorticotropic Hormone; Brain Neoplasms; Child; Child, Preschool; Cranial Irradiation; Gonadotropins; Human Growth Hormone; Humans; Hypothalamus; Pituitary Gland; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prolactin; ROC Curve; Thyrotropin; Time Factors; Treatment Outcome
PubMed: 27476159
DOI: 10.1007/s11864-016-0426-0 -
Endocrine Oct 2023Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.
BACKGROUND
Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.
OBJECTIVES
To assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up.
METHODS
All patients treated surgically with and without radiotherapy for NFPMs between 1987 and 2018 who had longer than six months follow-up were identified. Demographics, presentation, investigation, treatment, and outcomes were collected.
RESULTS
In total, 383 patients were identified. The median age was 57 years, with a median follow-up of 8 years. Preoperatively, 227 patients (227/375; 61%) had evidence of at least one pituitary deficiency. Anterior panhypopituitarism was more common in men (p = 0.001) and older patients (p = 0.005). Multiple hormone deficiencies were associated with large tumours (p = 0.03). Patients treated with surgery and radiotherapy had a higher incidence of all individual pituitary hormone deficiency, anterior panhypopituitarism, and significantly lower GH, ACTH, and TSH deficiencies free survival probability than those treated with surgery alone. Recovery of central hypogonadism, hypothyroidism, and anterior panhypopituitarism was also less likely to be reported in those treated with surgery and radiotherapy. Those with preoperative hypopituitarism had a higher risk of pituitary impairment at latest review than those presented with normal pituitary function (p = 0.001).
CONCLUSION
NFPMs are associated with a significant degree of hypopituitarism at time of diagnosis and post-therapy. The combination of surgery and radiotherapy is associated with a higher risk of pituitary dysfunction. Recovery of pituitary hormone deficit may occur after treatment. Patients should have regular ongoing endocrine evaluation post-treatment to assess changes in pituitary function and the need for long-term replacement therapy.
Topics: Male; Humans; Middle Aged; Retrospective Studies; Hypopituitarism; Pituitary Gland; Pituitary Neoplasms; Pituitary Hormones; Hypothyroidism
PubMed: 37389717
DOI: 10.1007/s12020-023-03434-3