促性腺激素释放激素受体及其基因表达调控

促性腺激素释放激素（ＧｎＲＨ,ＬＨＲＨ）在体内的重要功能是由ＧｎＲＨ受体介导的。ＧｎＲＨ受体是近年神经分内分泌和生殖生物学研究的热点之一,本文从ＧｎＲＨ受体的分子结构,ＧｎＲＨ受体基因表达调控,ＧｎＲＨ受体分布及表达,调节ＲｎＲＨ受体的因素以及ＧｎＲＨ受体介导的细胞信号转导等几个方面对ＧｎＲＨ受体近年来的研究进展进行了综述,对ＧｎＲＨ受体的研究,将有助于人们进一步了解ＧｎＲＨ受体在生殖调节和恶性肿     

Pituitary gonadotropin-releasing hormone (GnRH) receptor: structure, distribution and regulation of expression

Reproduction in mammals is controlled by interactions between the hypothalamus, anterior pituitary and gonads. Interaction of GnRH with its cognate receptor is essential to regulating reproduction. Characterization of the structure, distribution and expression of GnRH receptors (GnRH-R) has furthered our understanding of the physiological consequences of GnRH stimulation of pituitary gonadotropes. Based on the putative topology of the amino acid sequence of the GnRH-R and point mutation studies, key elements of the GnRH-R have been identified to play a role in ligand recognition and binding, G-protein activation and internalization. Normally, reproductive function is mediated by GnRH-R expressed only on the membranes of pituitary gonadotropes. The density of GnRH-R on gonadotropes determines their ability to respond to GnRH. This density is highest just prior to ovulation and likely is important for complete expression of the pre-ovulatory surge of LH. Therefore, knowledge regarding what regulates the density of GnRH-R is essential to understanding changes in pituitary sensitivity to GnRH and ultimately, to expression of the LH surge. Regulation of GnRH-R gene expression is influenced by a multitude of factors including gonadal steroid hormones, inhibin, activin and perhaps most importantly GnRH itself.     

Membrane progesterone receptor expression in mammalian tissues: A review of regulation and physiological implications

The recent discovery of a novel, membrane localized progestin receptor (mPR) unrelated to the classical progesterone receptor (PR) in fishes and its subsequent identification in mammals suggests a potential mediator of non-traditional progestin actions, particularly in tissues where PR is absent. While early studies on mPR focused on final oocyte maturation in fishes, more current studies have examined mPRs in multiple mammalian systems in both reproductive and non-reproductive tissues as well as in diseased tissues. Here we review the current data on mPR in mammalian systems including male and female reproductive tracts, liver, neuroendocrine tissues, the immune system and breast and ovarian cancer. We also provide new data demonstrating mPR expression in the RAW 264.7 immune cell line and bone marrow-derived macrophages as well as mPR expression and downstream gene regulation in ovarian cancer cells.     

Neuroendocrine function in Huntington's disease: dopaminergic regulation of prolactin release.

Plasma prolactin levels were measured in 7 patients with Huntington's disease (HD) and 8 age matched controls after the random, oral administration of 1) placebo, 2) chlorpromazine 100 mg, 3) carbidopa 50 mg followed by levodopa 200 mg, and 4) bromocriptine 1 mg. After placebo, HD patients had significantly higher prolactin levels than controls at all times except 180, 240, and 360 minutes. Controls showed a significant suppression of prolactin release at 180 and 240 minutes after levodopa/carbidopa and at 180, 240, and 360 minutes after bromocriptine. In contrast, HD patients demonstrated no change after both levodopa/carbidopa and bromocriptine. Both groups showed a sustained elevation after CPZ, but despite having an initially higher baseline and an earlier response, the maximum prolactin levels of HD patients were significantly less than those of controls.This data suggest that HD patients may have a diminished number of hypothalamic-pituitary dopamine receptors for the regulation PRL secretion.     

Altered release of carnitine palmitoyltransferase activity by digitonin from liver mitochondria of rats in different physiological states.

The release of carnitine palmitoyltransferase (CPT) activity from rat liver mitochondria by increasing concentrations of digitonin was studied for mitochondrial preparations from fed, 48 h-starved and diabetic animals. A bimodal release of activity was observed only for mitochondria isolated from starved and, to a lesser degree, from diabetic rats, and it appeared to result primarily from the enhanced release of approx. 40% and 60%, respectively, of the total CPT activity. This change in the pattern of release was specific to CPT among the marker enzymes studied. For all three types of mitochondria there was no substantial release of CPT concurrently with that of the marker enzyme for the soluble intermembrane space, adenylate kinase. These results illustrate that the bimodal pattern of release of CPT reported previously for mitochondria from starved rats [Bergstrom & Reitz (1980) Arch. Biochem. Biophys. 204, 71-79] is not an immutable consequence of the localization of CPT activity on either side of the mitochondrial inner membrane. Sequential loss of CPT I (i.e. the overt form) from the mitochondrial inner membrane did not affect the concentration of malonyl-CoA required to effect fractional inhibition of the CPT I that remained associated with the mitochondria. The results are discussed in relation to the possibility that altered enzyme-membrane interactions may account for some of the altered regulatory properties of CPT I in liver mitochondria of animals in different physiological states.     

The cardiac expression of Mas receptor is responsive to different physiological and pathological stimuli

The Mas protooncogene encodes a G protein-coupled receptor that has been described as a functional receptor for the cardioprotective fragment of the renin-angiotensin system (RAS), Angiotensin (Ang)-(1-7). The aim of this current study was to evaluate the responsiveness of Mas expression in hearts during different physiological and pathological conditions in rats. Physical training was considered a physiological condition, while isoproterenol-induced hypertrophy, myocardial infarction and DOCA-salt model of hypertension were used as pathological models of heart injury. The expression of Mas was analyzed by western blotting. Although swim-trained rats presented significant cardiac hypertrophy, our physical training protocol was unable to induce changes in the expression of Mas. On the other hand, cardiac hypertrophy and damage elicited by isoproterenol treatment led to a reduction in Mas expression. Myocardial infarction also significantly decreased the expression of Mas after 21 days of myocardial ischemia. Additionally, Mas expression levels were increased in hearts of DOCA-salt rats. Our present data indicate that Mas expression is responsive to different pathological stimuli, thereby suggesting that Mas receptor is involved in the homeostasis of the heart, as well as in the establishment and progression of cardiac diseases.     

Regulation of gonadotropin release, GnRH receptors, and gonadotrope responsiveness: a role for GnRH receptor microaggregation

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from pituitary gonadotrope cells. Additional receptor-mediated actions of the releasing hormone include homologous regulation of both the GnRH receptor and of cell responsiveness. While it is apparent that the release mechanism is Ca²⁺ mediated, it remains unclear how this receptor-mediated action is integrated with regulation of the receptor and with cell responsiveness. It is the purpose of this review to describe the requirements for gonadotropin release as well as for receptor and response regulation in order to prepare an integrated model for these actions of the releasing hormone.     

Ligand-specific receptor states: implications for opiate receptor signalling and regulation

Opiate drugs produce their effects by acting upon G protein coupled receptors (GPCRs) and although they are among the most effective analgesics available, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence, respiratory depression, nausea and constipation. As a class, opiates share a common profile of unwanted effects but there are also significant differences in ligand liability for producing these actions. A growing number of studies show that GPCRs may exist in multiple active states that differ in their signalling and regulatory properties and which may distinctively bind different agonists. In this review we summarize evidence supporting the existence of multiple active conformations for MORs and DORs, analyze information favouring the existence of ligand-specific receptor states and assess how ligand-selective efficacy may contribute to the production of longer lasting, better tolerated opiate analgesics.     

Nuclear bodies in bovine mammary gland in different physiological states

The frequency of nuclear bodies was determined in epithelial cells of mammary ductules or alveoli, milk cistern and teat sinus of virgin heifers, non-lactating cows and cows in early lactation. The determined frequency was within the range 12–16% with the single exception of the epithelial cells of secretory alveoli of lactating cows, in which the frequency was 3 %. These data support the concept that nuclear bodies are normal nuclear organelles which can respond to altered physiological conditions.     

Somatostatin receptor subtype-dependent regulation of nitric oxide release: involvement of different intracellular pathways

We reported previously that, in addition to direct effects, somatostatin (SST) affects tumor growth inhibiting the tumoral neoangiogenesis, via an interference with NO synthesis. Here, we analyzed the effects of SST on nitric oxide (NO) production induced by different agonists [basic fibroblast growth factor (bFGF), insulin, cholecystokinin (CCK)] and the intracellular signaling involved, using Chinese hamster ovary-k1 cells stably transfected with individual SSTR1-SSTR4. bFGF and insulin induced endothelial nitric oxide synthase activity via the generation of ceramide or the Akt-dependent phosphorylation of endothelial nitric oxide synthase, respectively. CCK regulates neuronal nitric oxide synthase activity in a Ca++-dependent manner. SST inhibited NO production stimulated by bFGF through SST receptor 1 (SSTR1), SSTR2, and SSTR3 and by CCK through SSTR2 and SSTR3. In all the cell lines, SST treatment did not modify NO synthesis induced by insulin. SSTR4 activation was not effective on any of the stimuli tested. The effects on bFGF-induced NO production were downstream from receptor phosphorylation and ceramide synthesis. SSTR2 and -3 on CCK activity were related to the inhibition of intracellular Ca++ mobilization, whereas the lack of effects on insulin was paralleled by the absence of SST activity on Akt phosphorylation. These data, identifying for the first time a selective receptor subtype-inhibitory role of SST on NO generation, may open new perspectives in the use of SST agonists to control tumoral angiogenesis.     

Evidence for changes in nuclear permeability during different physiological states

It was found that the nuclei of well-fed amoebae accumulate colloidal gold from the cytoplasm at a significantly greater rate than the nuclei of cells starved for five or nine days. The results are most likely due to a decrease in the permeability of the nuclear envelope during starvation. Evidence was obtained indicating that the permeability decrease is caused by a change in the functional properties of the pores, rather than a change in either pore size or number. These findings are consistent with the view that the nuclear pores are involved in regulating cellular activity.     

The macronuclear envelope ofTetrahymena pyriformis GL in different physiological states

Summary A simple formula is derived to calculate the nucleocytoplasmic RNA-Efflux per nuclear Pore complex per min (REP-rate) which is generally applicable both for growing and stationary eukaryotic cells. In actively growing cells this REP-rate is mainly dependent on the cytoplasmic RNA-pool, the number of RNA-transporting pores, and the growth constant of RNA. These parameters are determined in logarithmicTetrahymena pyriformis GL. In this organism, 45 molecules both of the larger ribosomal RNA (25s rRNA) and of the smaller (17s rRNA) are transported per pore per min from nucleus to cytoplasm. Pulse-label experiments with³H-uridine indicate that the 25s rRNA is obviously transferred more slowly to the cytoplasm than the 17s rRNA. We postulate a gating hypothesis on the regulation of the nucleocytoplasmic RNA-efflux by nuclear pore complexes. This gating hypothesis suggests that nucleopores are controlling points of secondary importance in the sequence of gene expression, and do not directly control the cytoplasmic protein synthesis in eukaryotic cells.     

Galectin genes: regulation of expression

In this review we have summarized the more recent studies on the expression of mammalian galectins. One interesting observation that can be made is that in most of microarrays and/or differential display analysis performed in recent years one or more galectins have been picked up. From a critical evaluation of the pertinent studies the main conclusion that can be drawn is that, although it is not yet clear whether the 14 galectins identified so far have functions in common, a striking common feature of all galectins is the strong modulation of their expression during development, differentiation stages and under different physiological or pathological conditions. This suggests that the expression of different galectins is finely tuned and possibly coordinated. In spite of these observations it is rather unexpected that very few studies have been performed on the molecular mechanisms governing the activity of galectin genes.