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Hormones regulate development, as well as many vital processes in the daily life of an animal. Many of these hormones are peptides that act at a higher hierarchical level in the animal with roles as organizers that globally orchestrate metabolism, physiology and behavior. Peptide hormones can act on multiple peripheral targets and simultaneously convey basal states, such as metabolic status and sleep-awake or arousal across many central neuronal circuits. Thereby, they coordinate responses to changing internal and external environments. The activity of neurosecretory cells is controlled either by (1) cell autonomous sensors, or (2) by other neurons that relay signals from sensors in peripheral tissues and (3) by feedback from target cells. Thus, a hormonal signaling axis commonly comprises several components. In mammals and other vertebrates, several hormonal axes are known, such as the hypothalamic-pituitary-gonad axis or the hypothalamic-pituitary-thyroid axis that regulate reproduction and metabolism, respectively. It has been proposed that the basic organization of such hormonal axes is evolutionarily old and that cellular homologs of the hypothalamic-pituitary system can be found for instance in insects. To obtain an appreciation of the similarities between insect and vertebrate neurosecretory axes, we review the organization of neurosecretory cell systems in Drosophila. Our review outlines the major peptidergic hormonal pathways known in Drosophila and presents a set of schemes of hormonal axes and orchestrating peptidergic systems. The detailed organization of the larval and adult Drosophila neurosecretory systems displays only very basic similarities to those in other arthropods and vertebrates. Electronic supplementary material The online version of this article (10.1007/s00441-020-03264-z) contains supplementary material, which is available to authorized users.

Aims/hypothesis The identification of novel targets that stimulate endogenous regeneration of beta cells would represent a significant advance in the treatment of patients with diabetes. The betatrophin hypothesis suggests that increased expression of angiopoietin-like protein 8 (ANGPTL8) induces dramatic and specific beta cell proliferation and subsequent beta cell mass expansion with improved glucose tolerance. In light of recent controversy, we further investigated the effects of ANGPTL8 overexpression on beta cell proliferation. Methods We performed hydrodynamic tail vein injections of green fluorescent protein (GFP) or Angptl8 (also known as Gm6484) DNA in multiple cohorts of mice of different ages. We employed state-of-the-art methods to comprehensively quantify beta cell mass and proliferation, controlling for mouse age, genetic strain, source of DNA injected, Angptl8 gene expression and proliferation markers. Results In two young and two aged cohorts of B6.129 mice, no substantial change in beta cell replication, mass or glucose homeostasis was observed following ANGPTL8 overexpression. Even in mice with extremely elevated Angptl8 expression (26-fold increase), beta cell replication was not significantly altered. Finally, we considered mice on the ICR background exactly as studied by Melton and colleagues, and still no beta cell mitogenic effect was detected following ANGPTL8 overexpression. Conclusion/interpretation ANGPTL8 does not stimulate beta cell replication in young or old mice. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3590-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Worldwide, the number of adults with type 2 diabetes has more than doubled since 1980 (Danaei et al. 2011). Why obesity is the main cause for this can be plausibly explained by knowledge of the underlying molecular mechanisms.

Several types of chemical messengers are employed by the nervous system for local or more diffuse signaling. Among these the peptides are the most diverse in structure and function. In nervous tissues they are typically produced by neurons or neurosecretory cells, and can therefore be specified as neuropeptides or peptide hormones, respectively. Additionally, many peptides are produced by endocrine cells or other cell types in different locations. In fact, the same peptide can be expressed by all these cell types in a given animal. Neuropeptides and peptide hormones are ubiquitous in the nervous and endocrine systems of all metazoans. Not only do these peptides exist in a large number of distinct molecular forms, they are also very diverse in their actions and signaling mechanisms. Thus, in a single animal species there may be more than a 100 different neuropeptides and peptide hormones (and their receptors), and each can have multiple functions. The peptides are encoded in the genome as parts of larger precursor proteins, referred to as prepropeptides. This direct coding means that when whole animal genomes have been sequenced the total inventory of neuropeptides and peptide hormones can be predicted. Such sequence data can also be used for analysis of neuropeptide evolution and show that some peptide sequences are well conserved across a broad range of species, whereas others display considerable variability and some are even unique to certain taxa. In this chapter we show that in some cases not only peptide sequences, but also the receptor structures and mechanisms of action and physiological functions can be conserved from invertebrates to vertebrates.

Ever since the seminal discovery of systemic wound signaling in tomato and potato plants by Green and Ryan (Science 1972), a number of candidate systemic wound signals have been proposed. These can be classified into three groups: (1) Chemical signals, including the alarm hormone systemin and other peptide hormones, jasmonic acid is a phytohormone, as well as reactive oxygen species (ROS); (2) physical signals, including electrical and hydraulic signals; and (3) herbivore-induced volatile compounds, including green leafy volatiles and terpenes. These signals are generated at or close to the site of herbivore-inflicted injury and systemically move to target tissues where they induce defense responses. Chemical and physical signals depend on the connectivity of the plant body, whereas volatile compounds are released into the airspace. Different plants with different morphologies and ecological niches employ different modes of systemic signaling.

Resistin is a mainly adipose-derived peptide hormone, that reduces insulin sensitivity in adipocytes, skeletal muscles and hepatocytes. Only in recent years resistin has been studied in liver disease and the regarding literature is very poor. According to recent studies considering resistin like a clinical biomarker in the assessment of liver cirrhosis, we propose an application of a finite mixture regression model with concomitant variable in order to individualize factors that influence resistin levels in patients affected by different virus hepatitis. The estimated model shows the existence of two separated components differing for the intercept and for some covariates; moreover high serum resistin levels do not seem to be associated with liver histological lesions by C virus, but only by B virus hepatitis.

There has been an extensive debate in behavioural biology to what extent the function and adaptive value of behavioural traits require, or are limited by, specific physiological processes triggered by hormones. The observation that testis size predicts mating systems suggested that testosterone may be an important proximate factor involved in the regulation of mating systems. Indeed, there is evidence that seasonal patterns of circulating testosterone are related to mating systems. Testosterone manipulations affect mating decisions in some, but not all species. In addition, the peptide hormones oxytocin and arginine vasopressin play a major role in pair-bond formation and the expression of different mating systems in mammals. Exciting recent studies indicated that changes in complex social behaviours may be based on the differential expression pattern of just one hormone receptor gene. Rather than social status itself, the process by which social status is achieved and maintained determines the physiological and psychosocial effects associated with a given social status. Current knowledge suggests that the relationship between behaviour and hormones can be quite complex. It also shows that the study of function and adaptive value of behavioural traits and hormonal processes is most successful if the links between the two are explicitly recognised.

Protein and peptide therapeuticals (PPTs) form a relatively recent class of active pharmaceutical ingredients (APIs) (Leader et al. 2008). Mostly, they consist of biotechnologically produced monoclonal antibodies and peptide hormones, but there are also examples isolated from natural tissues, as well as some chemically synthesised peptides. The monoclonal antibodies in particular are highly specific and therefore constitute precisely targeted APIs. In certain cases these PPTs may be covalently bound to long-chained polyethylene glycol (PEG) as so-called PEGylated PPTs, which show significantly prolonged elimination half-lives (Webster et al. 2007).

VIP and PACAP.- Biosynthesis of Cardiac Natriuretic Peptides.- Chromogranins A and B and Secretogranin II as Prohormones for Regulatory Peptides from the Diffuse Neuroendocrine System.- Neurotensin and Neuromedin N Are Differentially Processed from a Common Precursor by Prohormone Convertases in Tissues and Cell Lines.- Ghrelin: From Gene to Physiological Function.- Somatostatin and Somatostatin Receptors.- ACTH: Cellular Peptide Hormone Synthesis and Secretory Pathways.- Maturation of Secretory Granules.- Cell-Specific Precursor Processing.- Posttranslational Processing of Progastrin.- Glucagon and Glucagon-Like Peptides 1 and 2.

The singular gene for a peptide hormone is expressed not only in a specific endocrine cell type but also in other endocrine cells as well as in entirely different cells such as neurons, adipocytes, myocytes, immune cells, and cells of the sex-glands. The cellular expression pattern for each gene varies with development, time and species. Endocrine regulation is, however, based on the release of a given hormone from an endocrine cell to the general circulation from whose cappilaries the hormone reaches the specific target cell elsewhere in the body. The widespread expression of hormone genes in different cells and tissues therefore requires control of biogenesis and secretion in order to avoid interference with the function of a specific hormonal peptide from a particular endocrine cell. Several mechanisms are involved in such control, one of them being cell-specific processing of prohormones. The following pages present four examples of such cell-specific processing and the implications of the phenomenon for the use of peptide hormones as markers of diseases. Notably, sick cells – not least the neoplastic cells – often process prohormones in a manner different from that of the normal endocrine cells.

Adrenocorticotrophic hormone (ACTH) is derived from the prohormone, pro-opiomelanocortin (POMC). This precursor undergoes proteolytic cleavage to yield a number of different peptides which vary depending on the tissue. In the anterior pituitary, POMC is processed to ACTH by the prohormone convertase, PC1 and packaged in secretory granules ready for stimulated secretion. In response to stress, corticotrophin releasing hormone (CRH), stimulates release of ACTH from the pituitary cell which in turn causes release of glucocorticoids from the adrenal gland. In tissues, such as the hypothalamus and skin, ACTH is further processed intracellularly to alpha melanocyte stimulating hormone (alphaMSH) which has distinct roles in these tissues. The prohormone, POMC, is itself released from cells and found in the human circulation at concentrations greater than ACTH. While much is known about the tightly regulated synthesis of POMC, there is still a lot to learn about the mechanisms for differentiating secretion of POMC, and the POMC-derived peptides. Understanding what happens to the POMC released from cells will provide new insights into its function.

Mass spectrometric approaches have been used to determine various peptide hormones in sports drug testing. While insulin-like growth factor-1 (IGF-1) and its synthetic analogs are qualitatively and/or quantitatively measured by liquid chromatography–tandem mass spectrometry after immunoaffinity purification, methods of uncovering doping rule violations with illegal applications of human growth hormone (hGH) have not yet been established using mass spectrometry-based assays. However, substantial information on the heterogeneity of hGH, splice variants and post-translational modifications with respective locations as elucidated by mass spectrometry are of utmost importance for improving currently employed immunological procedures.

Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac peptides has only been elucidated during the last decade. The cellular synthesis including amino acid modifications and proteolytic cleavages has proven considerably more complex than initially perceived. Consequently, the elimination phase of the peptide products in circulation is not yet well characterized. An ongoing characterization of the molecular heterogeneity will help appreciate the biosynthetic capacity of the endocrine heart and could introduce new diagnostic possibilities. Notably, different biosynthetic products may not be equal markers of the same pathophysiological processes. An inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology.

Neuropeptides and kinins are important messengers in the nervous system and--on the basis of their anatomical localisation and the effects produced when the substances themselves are administered, to animals or to human subjects-a significant number of them have been suggested to have a role in pain and inflammation. Experiments in gene deletion (knock-out or null mutant) mice and parallel experiments with pharmacological receptor antagonists in a variety of species have strengthened the evidence that a number of peptides, notably substance P and calcitonin gene-related peptide (CGRP), and the kinins have a pathophysiological role in nociception. Clinical studies with non-peptide pharmacological antagonists are now in progress to determine if blocking the action of these peptides might have utility in the treatment of pain.