Does androgen influence prolactin secretion?

In both intact and castrated male and female rats, administration of the A-ring reduced androgen, dihydrotestosterone (DHT), consistently failed to stimulate prolactin (PRL) secretion although it inhibited LH release and, in males, stimulated ventral prostate growth. In intact females, but not in the other types of rat, DHT actually suppressed PRL release. These findings do not support generalizations, based entirely on findings with testosterone, that both "androgens" and estrogens exert stimulatory actions on PRL secretion. The distinct stimulatory effects of testosterone and its esters on PRL secretion seem attributable, not to their androgenic actions per se, but to the ability of testosterone to form estrogenic metabolites. This ability does not appear to be shared by the "pure" androgen, DHT.     

Type III secretion à la Chlamydia

Type III secretion (T3S) is a mechanism that is central to the biology of the Chlamydiaceae and many other pathogens whose virulence depends on the translocation of toxic effector proteins to cytosolic targets within infected eukaryotic cells. Biomathematical simulations, using a previously described model of contact-dependent, T3S-mediated chlamydial growth and late differentiation, suggest that chlamydiae contained in small non-fusogenic inclusions will persist. Here, we further discuss the model in the context of in vitro-persistent, stress-induced aberrantly enlarged forms and of recent studies using small molecule inhibitors of T3S. A general mechanism is emerging whereby both early- and mid-cycle T3S-mediated activities and late T3S inactivation upon detachment of chlamydiae from the inclusion membrane are crucial for chlamydial intracellular development.     

Hypothalamic regulation of pituitary secretion of luteinizing hormone—II feedback control of gonadotropin secretion

A general mathematical model describing the biochemical interactions of the hormones luteinizing hormone releasing hormone (LHRH), luteinizing hormone (LH) and testosterone (T) in the male is presented. The model structure consists of a negative feedback system of three ordinary differential equations, in which the qualitative behavior is either a stable constant equilibrium solution or oscillatory solutions. A specific realization of the model is used to describe the experimental observations of pulsatile hormone release, its experimental suppression, the onset of puberty, the effects of castration, and several other qualitative and quantitative results. This model is presented as a first step in understanding the physicochemical interactions of the hypothalamic-pituitary-gonadal axis. Based on a paper presented at the conference “Mathematics in the Medical Sciences”, Dalhousie University, Halifax, Nova Scotia, June, 1976.     

Short-term gland secretion in the African elephant: tourist disturbance or social interactions as source for secretion?

The temporal gland is an organ found exclusively in elephants, located midway between the eye and the ear. Hypotheses exist about what factors lead to the release of the secretion but so far few studies have taken place in the wild, especially of secretion in relation to behaviour. It has been suggested that the secretion serves in communication or that it is a symptom of stress. These hypotheses were tested by observing free-ranging elephants in Etosha National Park, Namibia. Factors considered were the impact of carnivores, of herds of other herbivores, of vehicles and of other elephants on the amount of secretion in focal elephant families. Neither other mammals nor tourists, recorded in terms of vehicles, seemed to affect secretion, but the secretion increased with the rate at which members of elephant families displaced each other. It is concluded that the secretion is predominantly related to social behaviour and less to factors extrinsic to the elephant herd.     

Understanding the mechanism of IL-1β secretion

The cytokine interleukin-1β (IL-1β) is a key mediator of the inflammatory response. Essential for the host-response and resistance to pathogens, it also exacerbates damage during chronic disease and acute tissue injury. It is not surprising therefore that there is a huge level of interest in how this protein is produced and exported from cells. However, the mechanism of IL-1β release has proven to be elusive. It does not follow the conventional ER-Golgi route of secretion. A literature full of disparate observations arising from numerous experimental systems, has contributed to a complicated mix of diverse proposals. Here we summarise these observations and propose that secretion of IL-1β occurs on a continuum, dependent upon stimulus strength and the extracellular IL-1β requirement.     

Does acetylcholinesterase secretion involve an ADAMs-like metallosecretase?

Summary The ADAMs (A Disintegrin And Metalloprotease-like) family is a large and rapidly expanding group of metallo-proteinases with structural similarity. The are normally characterized by the presence of a proteolytic domain and disintegrin and signalling domains. Although 21 ADAMs proteins have been already cloned to date, in most cases their natural substrates are unknown. The best characterized representative of the mammalian ADAMs family is the TNF-α converting enzyme (TACE). TACE is an integral membrane metalloproteinase that causes the secretion of the active form of TNF-α from its plasma membrane precursor and thus can be regarded as a membrane protein secretase. Secretion of membrane proteins is a very well documented biological phenomenon and was demonstrated for a diverse range of membrane proteins, two examples being angiotensin converting enzyme (ACE) and Alzheimer's amyloid precursor protein (APP). ACE and APP secretion was shown to possess substantial similarity with the secretion of TNF-α. In the present study, we have attempted to demonstrate that a metalloproteinase might be involved in the shedding of another membrane-bound protein—acetylcholinesterase (AChE). Secretion of AChE by human neuroblastoma SH-SY5Y cells was found to be inhibited by a selective hydroxamate metalloproteinase inhibitor batimastat (20 μM), and stimulated by carbachol (20 μM), which have previously been shown to regulate the activity of APP α-secretase in a similar manner. The role of ADAMs proteins in the shedding of molecules from the cell surface is discussed.     

Molecular quantification of Saccharomyces cerevisiae α-pheromone secretion

Saccharomyces cerevisiae yeast cells court each other by producing an attractive sex pheromone specific to their mating type. Cells detect the sex pheromone from potential mates using a well-defined intracellular signalling cascade that has become a model for studying signal transduction. In contrast, the factors contributing to the production of pheromone itself are poorly characterized, despite the widespread use of the S.?cerevisiae α-pheromone secretion pathway in industrial fungal protein expression systems. Progress in understanding pheromone secretion has been hindered by a lack of a precise and quantitative pheromone production assay. Here, we present an ELISA-based method for the quantification of α-pheromone secretion. In the absence of pheromone from the opposite mating type, we found that each cell secretes over 550 mature α-pheromone peptides per second; 90% of this total was produced from MF α1. The addition of a-pheromone more than doubled total α-pheromone secretion. This technique offers several improvements on current methods for measuring α-pheromone production and will allow detailed investigation of the factors regulating pheromone production in yeast.     

Diabetes and insulin secretion: whither KATP?

The critical involvement of ATP-sensitive potassium (KATP) channels in insulin secretion is confirmed both by the demonstration that mutations that reduce KATP channel activity underlie many if not most cases of persistent hyperinsulinemia, and by the ability of sulfonylureas, which inhibit KATP channels, to enhance insulin secretion in type II diabetics. By extrapolation, we contend that mutations that increase beta-cell KATP channel activity should inhibit glucose-dependent insulin secretion and underlie, or at least predispose to, a diabetic phenotype. In transgenic animal models, this prediction seems to be borne out. Although earlier genetic studies failed to demonstrate a linkage between KATP mutations and diabetes in humans, recent studies indicate significant association of KATP channel gene mutations or polymorphisms and type II diabetes. We suggest that further efforts to understand the involvement of KATP channels in diabetes are warranted.     

Is there leaderless protein secretion in plants?

The sugar alcohol mannitol and it’s catabolic enzyme mannitol dehydrogenase (MTD), in addition to welldocumented roles in metabolism and osmoprotection, may play roles in hostpathogen interactions. Research suggests that in response to the mannitol that pathogenic fungi secrete to suppress reactive oxygen-mediated host defenses, plants make MTD to catabolize fungal mannitol. Yet previous work suggested that pathogen-secreted mannitol is extracellular, while in healthy plants MTD is cytoplasmic. We have presented results showing that the normally cytoplasmic MTD is exported into the cell wall or extracellular space in response to the endogenous inducer of plant defense responses salicylic acid (SA). This SA-induced secretion is insensitive to brefeldin A, an inhibitor of Golgimediated protein transport. Together with the absence of MTD in Golgi stacks and the lack of a documented extracellular targeting sequence in the MTD protein, this suggests MTD is secreted by a non-Golgi, pathogen-activated secretion mechanism in plants. Here we discuss the potential significance of non-Golgi secretion in response to stress.Key words: protein secretion, mannitol metabolism, plant-pathogen interaction, extracellular space, apoplast     

Model for glucagon secretion by pancreatic α-cells

Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia). However, the mechanisms involved in this secretion are still not completely clear. Here, using experimental calcium time series obtained in mouse pancreatic islets at low and high glucose conditions, we propose a glucagon secretion model for α-cells. Our model takes into account that the resupply of releasable granules is not only controlled by cytoplasmic Ca2+, as in other neuroendocrine and endocrine cells, but also by the level of extracellular glucose. We found that, although calcium oscillations are highly variable, the average secretion rates predicted by the model fall into the range of values reported in the literature, for both stimulated and non-stimulated conditions. For low glucose levels, the model predicts that there would be a well-controlled number of releasable granules refilled slowly from a large reserve pool, probably to ensure a secretion rate that could last for several minutes. Studying the α-cell response to the addition of insulin at low glucose, we observe that the presence of insulin reduces glucagon release by decreasing the islet Ca2+ level. This observation is in line with previous work reporting that Ca2+ dynamics, mainly frequency, is altered by insulin. Thus, the present results emphasize the main role played by Ca2+ and glucose in the control of glucagon secretion by α-cells. Our modeling approach also shows that calcium oscillations potentiate glucagon secretion as compared to constant levels of this cellular messenger. Altogether, the model sheds new light on the subcellular mechanisms involved in α-cell exocytosis, and provides a quantitative predictive tool for studying glucagon secretion modulators in physiological and pathological conditions.     

Does acetylcholinesterase secretion involve an ADAMs-like metallosecretase?

The ADAMs (A Disintegrin And Metalloprotease-like) family is a large and rapidly expanding group of metalloproteinases with structural similarity. They are normally characterized by the presence of a proteolytic domain and disintegrin and signalling domains. Although 21 ADAMs proteins have been already cloned to date, in most cases their natural substrates are unknown. The best characterized representative of the mammalian ADAMs family is the TNF- converting enzyme (TACE). TACE is an integral membrane metalloproteinase that causes the secretion of the active form of TNF- from its plasma membrane precursor and thus can be regarded as a membrane protein secretase. Secretion of membrane proteins is a very well documented biological phenomenon and was demonstrated for a diverse range of membrane proteins, two examples being angiotensin converting enzyme (ACE) and Alzheimer's amyloid precursor protein (APP). ACE and APP secretion was shown to possess substantial similarity with the secretion of TNF-. In the present study, we have attempted to demonstrate that a metalloproteinase might be involved in the shedding of another membrane-bound protein – acetylcholinesterase (AChE). Secretion of AChE by human neuroblastoma SH-SY5Y cells was found to be inhibited by a selective hydroxamate metalloproteinase inhibitor batimastat (20 M), and stimulated by carbachol (20 M), which have previously been shown to regulate the activity of APP -secretase in a similar manner. The role of ADAMs proteins in the shedding of molecules from the cell surface is discussed.     

Type III secretion: what's in a name?

The term 'type III secretion' has seen widespread use. However, problems persist in nomenclature. We propose that the standard abbreviation for this kind of secretion should be 'T3S' and that 'type III secretion system' should be abbreviated to 'T3SS'. There is also a need for a new terminology to distinguish flagellar and non-flagellar type III secretion systems that reflects their common evolutionary ancestry but does not obscure their distinctive features. Finally, the use of the term 'type III secretion' to cover cytolysin-mediated translocation is to be deprecated because an authentic type III secretion system has already been described in gram-positive bacteria, namely the flagellar protein export apparatus.     

Type V protein secretion: simplicity gone awry?

Since its discovery in the late 1980's, the family of secreted proteins termed the autotransporters has been expanding continuously to become the largest group of secreted proteins in Gram-negative bacteria. The type V secretion pathway, which includes the autotransporters (type Va) together with the two-partner secretion system (type Vb) and the Oca family (type Vc), can be defined by secreted proteins that are (i) translocated across the outer membrane via a transmembrane pore formed by a beta-barrel and (ii) contain all the information required for translocation through the cell envelope. In the light of new discoveries and controversies in this research field, the secretion process of autotransporters, or the type Va secretion system, will be discussed here and placed in the context of the more general field of bacterial protein translocation.     

Insulin secretion: Feed-forward control of insulin biosynthesis?

It has long been accepted wisdom that insulin secreted from islet beta cells has either no effect, or an inhibitory feedback effect, on insulin synthesis and secretion. Recent work suggests, instead, that secreted insulin acts directly on beta cells, via its own receptor, to enhance insulin production in an autocrine feed-forward loop.     

Neuroendocrine control of follicle-stimulating hormone (FSH) secretion: II. Is follistatin-induced suppression of FSH secretion mediated via changes in activin availability and does it involve changes in gonadotropin-releasing hormone secretion?

The objective of the present study was to determine to what extent activin participates in setting the level of FSH secretion and if this regulation includes mediation via changes in GnRH secretion. We administered follistatin, the high-affinity binding protein for activin, to five ovariectomized sheep; we reasoned that the resultant binding of follistatin to activin should lower activin bioavailability and FSH secretion. Hypophyseal portal and peripheral blood samples were collected simultaneously at 10-min intervals for 18 h to measure GnRH, LH, FSH, and both activin-free and total follistatin. Six hours into collection, each ewe received 150 microg/kg i.v. of recombinant human follistatin-288. A week later, the same ewes were subjected to a second series of blood collections of similar length (time control). The FSH levels in pituitary portal blood were approximately 8-fold higher than those in the peripheral circulation. The FSH secretory patterns changed minimally during the time-control period. In contrast, follistatin had profound suppressive effects on FSH secretion. Maximal FSH suppression after FS-288 administration occurred at 5-6 h in the pituitary portal (65% suppression) and 9-10 h in the peripheral (48% suppression) circulation. Follistatin had no effect on GnRH or LH secretory patterns. Disappearance of total follistatin (i.e., free follistatin plus activin-bound follistatin) from the circulation was slower (P < 0.05) than that of free follistatin alone, suggesting that some of the follistatin was complexed with circulating activin, thus reducing the bioavailability of activin. The slower clearance of total follistatin and the lack of follistatin effects on GnRH secretion suggest that changes in activin bioavailability dictate the level of pituitary FSH secretion and that this is a pituitary-specific effect.     

Overproduction and secretion of α-ketoglutaric acid by microorganisms

This mini-review presents a summary of research results of biotechnological production of alpha-ketoglutaric acid (KGA) by bacteria and yeasts. KGA is of particular industrial interest due to its broad application scope, e.g., as building block chemical for the chemical synthesis of heterocycles, dietary supplement, component of infusion solutions and wound healing compounds, or as main component of new elastomers with a wide range of interesting mechanical and chemical properties. Currently KGA is produced via different chemical pathways, which have a lot of disadvantages. As an alternative several bacteria and yeasts have already been studied for their ability to produce KGA as well as for conditions of overproduction and secretion of this intermediate of the tricarboxylic acid cycle. The aim of this mini-review was to summarize the known data and to discuss the potentials of biotechnological processes of KGA production.