Journal of Neuroendocrinology最新文献

Growth hormone (GH) has a short half-life and declines abruptly following somatotropinoma surgery, enabling its prompt measurement as an indicator of surgical success. This study assesses the predictive value of early postoperative GH levels for 3-month and >1-year remission of acromegaly. We conducted a retrospective search in our database of patients who had undergone transsphenoidal surgery of GH-secreting pituitary adenoma from January 2011 to June 2022. Only the patients who underwent the first pituitary surgery and had GH measurements on the fifth postoperative day were included. The 3-month and >1-year remission of acromegaly was defined as achieving the GH nadir of <0.4 μg/L during an oral glucose tolerance test and maintaining normal insulin-like growth factor 1 levels at the initial follow-up visit 3 months after surgery and throughout at least the first year postoperation. We included 63 patients in the analysis, with a median follow-up of 51.8 (13–155) months. The 3-month remission was achieved in 42 (66.7%) patients, and >1-year remission without additional therapy in 38 (60.3%) patients. Those who achieved >1-year remission had significantly lower fifth-day postoperative GH levels (0.59 [0.09–8.92] vs. 2.63 [0.25–24.64] μg/L, p < .001). Receiver-operating characteristic analysis revealed a significant value of fifth-day postoperative GH levels regarding the prediction of 3-month (area under the curve [AUC], 0.834; p < .0001) and >1-year (AUC, 0.783; p < .0001) acromegaly remission. The GH threshold of ≤1.57 μg/L yielded a sensitivity of 90.5% and a specificity of 71.4% at 3 months and 89.5% sensitivity and 60% specificity at the >1-year remission, respectively. Notably, all patients with fifth-day postoperative GH levels ≤0.23 μg/L exhibited remission of acromegaly throughout the follow-up period. Early postoperative GH measurement could be a reliable predictor of both 3-month and >1-year remission of acromegaly.

The prolactin receptor (Prlr) is widely expressed in the brain, particularly in the hypothalamus. Prolactin also has an increasing range of well-characterised effects on central nervous system function. Because of this, over many years, there has been interest in whether the hormone itself is also expressed within the brain, perhaps acting as a neuropeptide to regulate brain function via its receptor in neurons. The aim of this invited review is to critically evaluate the evidence for brain production of prolactin. Unlike the evidence for the Prlr, evidence for brain prolactin is inconsistent and variable. A range of different antibodies have been used, each characterising a different distribution of prolactin-like immunoreactivity. Prolactin mRNA has been detected in the brain, but only at levels markedly lower than seen in the pituitary gland. Importantly, it has largely only been detected by highly sensitive amplification-based techniques, and the extreme sensitivity means there is a risk of false-positive data. Modern in situ hybridisation methods and single-cell RNA sequencing have not provided supporting evidence, but it is hard to prove a negative! Finally, I acknowledge and discuss the possibility that prolactin might be produced in the brain under specific circumstances, such as to promote a neuroprotective response to cell damage. Collectively, however, based on this analysis, I have formed the opinion that brain production of prolactin is unlikely, and even if occurs, it is of little physiological consequence. Most, if not all of the brain actions of prolactin can be explained by pituitary prolactin gaining access to the brain.

The type II gonadotropin-releasing hormone (GnRH-II) was first discovered in chicken (Gallus gallus) brain and then shown to be present in many vertebrates. Indeed, its structure is conserved unchanged throughout vertebrate evolution from teleost fish through to mammals suggesting a crucial function. Yet the functional significance has been largely unexplored. Studies in comparative endocrinology show that the GnRH-II system is differentially functional in mammalian species. Intact GnRH-II neuropeptide and receptor genes (GnRH2 and GnRH receptor 2 GnRHR2) occur in marmoset monkeys (Callithrix jacchus), musk shrews (Suncus murinus) and pigs (Sus scrofa). However, one or other or both of these genes are inactivated in other species, where mutations or remnants affecting GnRH2 neuropeptide and/or type II GnRHR exons are retained in conserved genomic loci. New data from DNA sequencing projects facilitate extensive analysis of species-specific variation in these genes. Here, we describe GnRH2 and GnRHR2 genes spanning a collection of 21 taxonomic orders, encompassing around 140 species from Primates, Scandentia, Eulipotyphla, Rodentia, Lagomorpha, Artiodactyla, Carnivora, Perissodactyls, Pholidota, Chiroptera, Afrotheria, Xenarthra and Marsupialia. Intact coding exons for both GnRH2 and GnRHR2 occur in monkeys, tree shrews, shrews, moles, hedgehogs, several rodents (degu, kangaroo-rat, pocket mouse), pig, pecarry and warthog, camels and alpaca, bears, Weddell seal, hyena, elephant, aardvark and marsupials. Inactivating mutations affecting GnRH2 and GnRHR2, some located at conserved sites within exons, occur in species of primates, most rodents, lagomorphs, bovidae, cetaceans, felidae, canidae and other carnivora, pangolins, most bats, armadillo, brushtail and echidna. A functional GnRH-II system appears retained within several taxonomic families of mammals, but intact retention does not extend to whole taxonomic orders. Defining how endogenous GnRH-II neuropeptide operates in different mammals may afford functional insight into its actions in the brain, especially as, unlike the type I GnRH system, it is expressed in the mid brain and not the hypothalamus.

Kisspeptins are essential regulators of the reproductive axis, with capacity to potently activate gonadotropin-releasing hormone neurons, acting also as central conduits for the metabolic regulation of fertility. Recent evidence suggests that kisspeptins per se may also modulate several metabolic parameters, including body weight, food intake or energy expenditure, but their actual roles and site(s) of action remain unclear. We present herein a series of studies addressing the metabolic effects of central and peripheral administration of kisspeptin-10 (Kp-10; 1 nmol and 3 nmol daily, respectively) for 11 days in mice of both sexes. To assess direct metabolic actions of Kp-10 versus those derived indirectly from its capacity to modulate gonadal hormone secretion, kisspeptin effects were tested in adult male and female mice gonadectomized and supplemented with fixed, physiological doses of testosterone or 17β-estradiol, respectively. Central administration of Kp-10 decreased food intake in male mice, especially during the dark phase (~50%), which was accompanied by a reduction in total and nocturnal energy expenditure (~16%) and locomotor activity (~70%). In contrast, opposite patterns were detected in female mice, with an increase in total and nocturnal locomotor activity (>65%), despite no changes in food intake or energy expenditure. These changes were independent of body weight, as no differences were detected in mice of both sexes at the end of Kp-10 treatments. Peripheral administration of Kp-10 failed to alter any of the metabolic parameters analyzed, except for a decrease in locomotor activity in male mice and a subtle increase in 24 h food intake in female mice, denoting a predominant central role of kisspeptins in the control of energy metabolism. Finally, glucose tolerance and insulin sensitivity were not significantly affected by central or peripheral treatment with Kp-10. In conclusion, our data reveal a potential role of kisspeptins in the control of key metabolic parameters, including food intake, energy expenditure and locomotor activity, with a preferential action at central level, which is sex steroid-independent but sexually dimorphic.

Here, we reflect on the long career in neuroendocrinology of a single, highly productive scientist (‘Bob’ Millar), by analysing his oeuvre of published papers through the lens of citation metrics. We use citation network analysis in a novel manner to identify the specific topics to which his papers have made a particular contribution, allowing us to compare the citations of his papers with those of contemporary papers on the same topic, rather than on the same broad field as generally used to normalise citations. It appears that citation rates are highest for topics on which Bob has published a relatively large number of papers that have become core to a tightly-knit community of authors that cite each other. This analysis shows that an author's impact depends on the existence of a receptive community that is alert to the potential utility of papers from that author, and which uses, amplifies, extends and qualifies the contents of their papers—activities that entail reciprocal citation between authors. The obvious conclusion is that a scientist's impact depends on the use that his or her contemporaries make of his or her contributions, rather than on the contributions in themselves.

In teleosts, GnRH1 neurons stand at the apex of the Hypothalamo-Pituitary-Gonadal (HPG) axis, which is responsible for the production of sex steroids by the gonads (notably, androgens). To exert their actions, androgens need to bind to their specific receptors, called androgen receptors (ARs). Due to a teleost-specific whole genome duplication, A. burtoni possess two AR paralogs (ARα and ARβ) that are encoded by two different genes, ar1 and ar2, respectively. In A. burtoni, males stratify along dominance hierarchies, in which an individuals' social status determines its physiology and behavior. GnRH1 neurons have been strongly linked with dominance and circulating androgen levels. Similarly, GnRH3 neurons are implicated in the display of male specific behaviors. Some studies have shown that these GnRH neurons are responsive to fluctuations in circulating androgens levels, suggesting a link between GnRH neurons and ARs. While female A. burtoni do not naturally form a social hierarchy, their reproductive state is positively correlated to androgen levels and GnRH1 neuron size. Although there are reports related to the expression of ar genes in GnRH neurons in cichlid species, the expression of each ar gene remains inconclusive due to technical limitations. Here, we used immunohistochemistry, in situ hybridization chain reaction (HCR), and spatial transcriptomics to investigate ar1 and ar2 expression specifically in GnRH neurons. We find that all GnRH1 neurons intensely express ar1 but only a few of them express ar2, suggesting the presence of genetically-distinct GnRH1 subtypes. Very few ar1 and ar2 transcripts were found in GnRH2 neurons. GnRH3 neurons were found to express both ar genes. The presence of distinct ar genes within GnRH neuron subtypes, most clearly observed for GnRH1 neurons, suggests differential control of these neurons by androgenic signaling. These findings provide valuable insight for future studies aimed at disentangling the androgenic control of GnRH neuron plasticity and reproductive plasticity across teleosts.

Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1–3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.

Pituitary adenomas are very common representing 18.1% of all brain tumors and are the second most common brain pathology. Transsphenoidal surgery is the mainstay of treatment for all pituitary adenomas except for prolactinomas which are primarily treated medically with dopamine agonists. A thorough endocrine evaluation of pituitary adenoma preoperatively is crucial to identify hormonal compromise caused by the large sellar mass, identifying prolactin-producing tumors and comorbidities associated with Cushing and acromegaly to improve patient care and outcome. Transsphenoidal surgery is relatively safe in the hands of experienced surgeons, but still carries a substantial risk of causing hypopituitarism that required close follow-up in the immediate postoperative period to decrease mortality. A multidisciplinary team approach with endocrinologists, ophthalmologists, and neurosurgeons is the cornerstone in the perioperative management of pituitary adenomas.