[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

[Diagnosis and new treatment options for pituitary adenomas].

Currently, the treatment of pituitary adenomas is inextricably linked with transsphenoidal neurosurgical intervention. Modern technologies used in surgery for this pituitary pathology, such as endoscopy using angled optics, as well as the use of specialized instruments, sealing and hemostatic materials, increase the effectiveness of surgical treatment of pituitary adenomas and reduce the incidence of intraand postoperative complications. The development of radiation methods of diagnostics, such as MRI, makes it possible to more accurately identify the formation of the pituitary gland, assess its size, direction of growth, and the degree of invasion of surrounding tissues. The authors of the article described in detail the modern technique of transsphenoidal removal of pituitary adenoma using an endoscope. Each stage of the operation is described step by step, taking into account various anatomical features and illustrated. This article discusses the MRI characteristics of pituitary adenomas: size of the tumor, the direction of its growth, the degree of invasion of the cavernous sinuses, the compression effect on the structures of the chiasmal-sellar region. The use of treatment methods, knowledge of the features of MRI diagnostics described in this article greatly increase the effectiveness of the treatment of patients with pituitary adenomas and reduce the risk of complications after neurosurgical intervention in such patients.

Measuring the variability of local characteristics in complex networks: Empirical and analytical analysis.

We examine the dynamics for the average degree of a node's neighbors in complex networks. It is a Markov stochastic process, and at each moment of time, this quantity takes on its values in accordance with some probability distribution. We are interested in some characteristics of this distribution: its expectation and its variance, as well as its coefficient of variation. First, we look at several real communities to understand how these values change over time in social networks. The empirical analysis of the behavior of these quantities for real networks shows that the coefficient of variation remains at high level as the network grows. This means that the standard deviation and the mean degree of the neighbors are comparable. Then, we examine the evolution of these three quantities over time for networks obtained as simulations of one of the well-known varieties of the Barabási-Albert model, the growth model with nonlinear preferential attachment (NPA) and a fixed number of attached links at each iteration. We analytically show that the coefficient of variation for the average degree of a node's neighbors tends to zero in such networks (albeit very slowly). Thus, we establish that the behavior of the average degree of neighbors in Barabási-Albert networks differs from its behavior in real networks. In this regard, we propose a model based on the NPA mechanism with the rule of random number of edges added at each iteration in which the dynamics of the average degree of neighbors is comparable to its dynamics in real networks.

[Cyclic Cushing's syndrome: difficulties of diagnostic search and choice of treatment tactics. A clinical case].

Cyclic Cushing's syndrome is a pathological condition characterized by alternating periods of excessive cortisol secretion with corresponding clinical manifestations and periods of spontaneous remission of the disease.To diagnose Cyclic Cushing's syndrome it is necessary to record at least three episodes of excessive cortisol secretion alternating with periods of normalization of its production.In most cases, this pathology is diagnosed in patients with ACTH-secreting pituitary tumor, however, there are rare cases of cyclic hypercorticism with ectopic ACTH secretion by tumors of different localization and without verification of pathological hormonal secretion focus. In addition, cyclic hyperproduction of cortisol can be also observed in ACTH-independent Cushing's syndrome associated with the presence of corticosteroma or adrenal hyperplasia. The exact causes and mechanisms of the cyclic hypercorticism are currently insufficiently studied.Due to the atypical course of the disease, the unpredictability of the occurrence of a new «cycle¼, the variability of its duration and manifestations (not only in different patients, but also in the same patient), verification of the diagnosis and determination of treatment tactics may be difficult in the daily practice of specialists, and the prevalence of this condition can be undervalued.

[Thyrotropin-secreting pituitary adenomas: clinical features and results of treatment in 45 patients].

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSH-PA) are a rare cause of thyrotoxicosis and account for 0.5-2% of all pituitary adenomas. Taking into account the rarity of the disease, it is extremely important to analyze each case of TSH-PA. AIM: To analyze the clinical characteristics and treatment outcomes of patients with TSH-PA, as well as to determine preoperative and early postoperative factors that predict long-term remission. MATERIALS AND METHODS: In a single-center retrospective study we analyzed clinical signs, laboratory and instrumental studies, as well as the treatment outcomes of patients with TSH-PA from 2010 to 2023. Preoperative factors, as well as TSH level measured on day 3 postoperatively, were evaluated for their ability to predict long-term remission when comparing groups of patients with and without remission. RESULTS: The study included 45 patients with TSH-PA (14 men, 31 women), with a median age of 45 years [30; 57]. The most common clinical manifestations of TSH-PA were: cardiac arrhythmia in 37 (82.2%) patients, thyroid pathology in 27 (60%), neurological disorders in 24 (53.35%). Most PAs were macroadenomas (n=35, 77.8%). Preoperatively, 28 (77.8%) patients received somatostatin analogs, and 20 (71.4%) patients were euthyroid at the time of surgery. Surgical treatment was performed in 36 (80%) patients, postoperative remission was achieved in 31 cases (86.1%). Administration of somatostatin analogues to patients with no remission/relapse after surgery lead to the remission in 100% of cases (4/4). A 1 mm increase in PA size raised the odds of recurrence/no remission by 1.15-fold,and PA invasion during surgery - by  5.129 fold. A TSH level on day 3 postoperatively above 0.391 mIU/L (AUC, 0.952; 95% CI 0.873-1.000; standard error 0.04; p<0.001) identifies patients with relapse/absence of remission after surgical treatment (sensitivity = 100%, specificity = 88.9%). CONCLUSION: The TSH-PA in the structure of PAs is extremely rare, and as a result, most of them are misdiagnosed and detected already at the stage of macroadenoma. The most effective method of treatment is transnasal transsphenoidal adenomectomy. Somatostatin analogues can be used as second-line therapy if surgical treatment is ineffective. We have proposed a possible model for postoperative TSH levels (>0.391 mU/l) to predict recurrence of TSH-PA, which requires validation on an expanded number of cases.

[Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly].

BACKGROUND: Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. AIM: To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness. MATERIALS AND METHODS: A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples. RESULTS: The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%). CONCLUSION: Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.

Molecular Mechanisms of Muscle Tone Impairment under Conditions of Real and Simulated Space Flight.

Kozlovskaya et al. [1] and Grigoriev et al. [2] showed that enormous loss of muscle stiffness (atonia) develops in humans under true (space flight) and simulated microgravity conditions as early as after the first days of exposure. This phenomenon is attributed to the inactivation of slow motor units and called reflectory atonia. However, a lot of evidence indicating that even isolated muscle or a single fiber possesses substantial stiffness was published at the end of the 20th century. This intrinsic stiffness is determined by the active component, i.e. the ability to form actin-myosin cross-bridges during muscle stretch and contraction, as well as by cytoskeletal and extracellular matrix proteins, capable of resisting muscle stretch. The main facts on intrinsic muscle stiffness under conditions of gravitational unloading are considered in this review. The data obtained in studies of humans under dry immersion and rodent hindlimb suspension is analyzed. The results and hypotheses regarding reduced probability of cross-bridge formation in an atrophying muscle due to increased interfilament spacing are described. The evidence of cytoskeletal protein (titin, nebulin, etc.) degradation during gravitational unloading is also discussed. The possible mechanisms underlying structural changes in skeletal muscle collagen and its role in reducing intrinsic muscle stiffness are presented. The molecular mechanisms of changes in intrinsic stiffness during space flight and simulated microgravity are reviewed.

[A rare case of a functioning gonadotroph tumor accompanied by erythrocytosis in an elderly man].

Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically "silent" and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.

[Blood metabolome analysis for creating a digital image of a healthy person]. / Metabolomnyi analiz krovi dlia sozdaniia tsifrovogo obraza zdorovogo cheloveka.

In the frame of the work, data on the implementation of metabolomics tests in medicine have been systematized. Based on the obtained data, a set of protocols was proposed, the sequential realization of which makes it possible to conduct a blood metabolome analysis for medical purposes. Using this analysis and the number of blood samples from healthy volunteers, a prototype of a healthy person's metabolomic image has been developed; it allows visually and digitally to assess the compliance of the human blood metabolome with the norm. At the same time, 99% of the metabolic processes reflected in the blood plasma are estimated. If abnormalities are detected, the metabolomic image allows to get the value of these deviations of metabolic processes in digital terms.

Anticarcinogenic activity of blue fluorescent hexagonal boron nitride quantum dots: as an effective enhancer for DNA cleavage activity of anticancer drug doxorubicin.

Blue fluorescent hexagonal boron nitride quantum dots (h-BNQDs) of ∼10 nm size as an effective enhancer for DNA cleavage activity of anticancer drug doxorubicin (DOX) were synthesized using simple one-step hydrothermal disintegration of exfoliated hexagonal boron nitride at very low temperature âˆ¼ 120 °C. Boron nitride quantum dots (BNQDs) at a concentration of 25 µg/ml enhanced DNA cleavage activity of DOX up to 70% as checked by converting supercoiled fragment into nicked circular PBR322 DNA. The interaction of BNQDs with DOX is proportional to the concentration of BNQDs, with binding constant K b ∼0.07338 µg/ml. In addition, ab initio theoretical results indicate that DOX is absorbed on BNQDs at the N-terminated edge with binding energy -1.075 eV and prevented the normal replication mechanisms in DNA. BNQDs have been shown to kill the breast cancer cell MCF-7 extensively as compared with the normal human keratinocyte cell HaCaT. The cytotoxicity of BNQDs may be correlated with reduced reactive oxygen species level and increased apoptosis in MCF-7 cells, which may be liable to enhance the anticancerous activity of DOX. The results provide a base to develop BNQD-DOX as a more effective anticancer drug.

[An ovarian hyperstimulation syndrome caused by gonadotropinoma in a young woman].

From 14 to 54% of all pituitary adenomas are nonfunctioning pituitary adenomas (NPAs), their prevalence is estimated as 7.041.3 cases per 100 000 population. The most common type of NPAs (73% of cases) are gonadotropinomas. In most cases, gonadotropinoma is characterized by secretion of biologically inactive hormones, so the release of gonadotropins does not lead to the development of any clinical symptoms. For this reason the diagnosis of gonadotropinomas is most often performed on the basis of immunohistochemical analysis. However, in rare cases, gonadotropinomas secrete biologically active hormones, most often follicle-stimulating (FSH). Ovarian hyperstimulation syndrome due to gonadotropin-secreting pituitary tumors occurs in about 3% of women with hormonally inactive pituitary adenomas at reproductive age and in 8% of patients with verified gonadotropinomas. This clinical case describes a young patient with a rare pathology: FSH/LH-secreting macroadenoma of the pituitary, which led to the development of ovary hyperstymulation symdrome. The diagnosis of pituitary adenoma was performed due to the identified hyperprolactinemia one month before the development of visual impairment, which can be considered a late diagnosis. Surgical treatment of gonadotropinomy was carried out successfully and without complications, remission of the disease was achieved, visual function was restored, the patient successfully became pregnant.

The Differential Expression of Adhesion Molecule and Extracellular Matrix Genes in Mesenchymal Stromal Cells after Interaction with Cord Blood Hematopoietic Progenitors.

The dynamics of the expression of genes encoding adhesion molecules, molecules of the connective tissue matrix, and its remodeling enzymes was studied in multipotent mesenchymal stromal cells (MSCs) from human adipose tissue after interaction with cord blood hematopoietic progenitors (HSPCs). An upregulation of ICAM1 and VCAM1, directly proportional to the coculture time (24-72 h), was found. After 72 h of culturing, a downregulation of the genes encoding the majority of matrix molecules (SPP1; COL6A2,7A1; MMP1,3; TIMP1,3; and HAS1) and cell-matrix adhesion molecules (ITGs) was revealed. The detected changes may ensure the realization of the stromal MSC function due to improvement of adhesion and transmigration of HSPCs into the subcellular space.

Radiation situation dynamics at the Andreeva Bay site for temporary storage of spent nuclear fuel and radioactive waste over the period 2002-2016.

The Coastal Technical Base (CTB) №569 at Andreeva Bay was established in the early 1960s and intended for the refueling of nuclear submarine reactors and temporary storage of spent nuclear fuel (SNF) and radioactive waste (RW). In 2001, the base was transferred to the Russian Ministry for Atomic Energy and the site remediation began. The paper describes in detail the radiation situation change at the technical site in Andreeva Bay from 2002-2016, the period of preparation for the most critical phase of remedial work: removal of spent fuel assemblies. The analysis of aggregated indicators and data mining were used. The article suggests the best number and location of checkpoints needed to ensure sufficient accuracy of the radiation situation description. The fractal properties of the radiation field are studied using the Hurst index. The relationship between checkpoints was assessed using the method of searching for checkpoint communities. The decrease in the integral of the ambient dose equivalent rate (ADER) at the technical site was evaluated by the method of time series decomposition. Three components of time series were identified: trend, seasonal and residual. The trend of the ADER integral over the technical site is a monotonic decreasing function, where the initial and final values differ tenfold. Taking into account that 137Cs dominates the radiation situation on-site, it is clear that the ADER due to the radionuclide decay will have decreased by 1.4 times. It is estimated that only a small proportion of 137Cs has migrated off-site. Therefore, approximately a sevenfold decrease in dose rate is mainly due to remediation activities of personnel. During the year, the seasonal component varies the ADER integral by a factor of two, due to snowfall. The residual component reflects the uncertainty of the ADER integral calculation and phases of active SNF and RW management. The methods developed are used to support the optimization of remediation work as well as regulatory supervision of occupational radiation protection.

Effects of endogenous hypercortisolism on bone mRNA and microRNA expression in humans.

Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. INTRODUCTION: The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing's disease (CD). METHODS: Bone samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 16 patients with clinically and biochemically evident CD and 10 patients with clinically non-functioning pituitary adenomas (NFPA) matched by sex, age, and body mass index. Quantitative polymerase chain reactions (qPCR) were used to examine the expression of genes (mRNA and miRs) known to be involved in bone remodeling regulation based on studies in animals and cell culture. RESULTS: Hypercortisolism was associated with the downregulation of genes involved in osteoblast function and maturation (ACP5, ALPL, BGLAP, COL1A1, COL1A2, BMP2, RUNX2, TWIST1). An excess of GC caused increased expression of Wnt-signaling antagonists (Dkk1, SOST) and changes in the levels of miRs that are known to suppress osteoblastogenesis (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) p < 0.05, q < 0.1. Interestingly, compensatory mechanisms were found in long-term hypercortisolism: upregulation of Wnt10b, LRP5, and LRP6; downregulation of SFRP4; changes in miRs involved in osteoblastogenesis (miR-210-5p, miR-135a-5p, miR-211, miR-23a-3p, miR-204-5p); and downregulation of genes associated with osteoclastogenesis. None of these changes prevented the suppression of bone formation. CONCLUSIONS: An excess of endogenous GC in humans suppresses bone formation through the upregulation of Wnt-signaling antagonists and dysregulation of miRs involved in mesenchymal stem-cell commitment. Both Wnt-signaling antagonists and miRs seem to be promising targets for further research in therapeutic intervention in glucocorticoid-induced osteoporosis.

[Increase of reparative potential of fabrics in sugar diabetes]. / Povyshenie reparativnogo potentsiala tkanei pri sakharnom diabete.

AIM: The purpose of the study was to study the effectiveness of the domestic drug Remaxol in reparative processes of laparotomic wound tissues in acute surgical abdominal pathology in patients with diabetes mellitus. MATERIAL AND METHODS: Clinical and laboratory studies were performed in 86 patients with acute surgical pathology of the abdominal cavity, 56 patients with type 1 diabetes mellitus, including 26 patients who received Remaxol in the early postoperative period (daily intravenous infusions of 400.0 ml for 5 days). RESULTS: It was established that diabetes mellitus is an important aggravating factor in the reparative process of tissue structures of a laparotomic wound. Undoubtedly, a significant factor in reducing the reparative potential of tissues is a significant activation of factors leading to membrane-destabilizing phenomena - oxidative stress, activation of phospholipases, hypoxia. The inclusion of Remaxol, which has antioxidant and antihypoxic effects, allows to significantly correct these pathogenetic components, which is the basis for optimization of the reparative process against the background of diabetes mellitus. There was a significant decrease in wound complications in the early postoperative period, a significant reduction in the stay of patients in the hospital.

Quantitative target proteomics of chromosome 13 human blood plasma proteins.

Quantitative proteomic analysis of 50 blood plasma samples of healthy volunteers who underwent a comprehensive medical examination and were found eligible for space flights was performed. As a result of directed mass spectrometric analysis, signals for 128 proteins, which accounted for nearly 40% of the total number of chromosome 13 gene products, were detected. The analysis of interindividual variation of concentrations of chromosome 13 proteins showed the presence of a pool comprising 41 proteins with a low variation (CV < 30%), which can potentially be used as biomarkers.

Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells from Umbilical Cord Blood.

Transplantation of umbilical cord blood cells is currently widely used in modern cell therapy. However, the limited number of hematopoietic stem and progenitor cells (HSPCs) and prolonged time of recovery after the transplantation are significant limitations in the use of cord blood. Ex vivo expansion with various cytokine combinations is one of the most common approaches for increasing the number of HSPCs from one cord blood unit. In addition, there are protocols that enable ex vivo amplification of cord blood cells based on native hematopoietic microenvironmental cues, including stromal components and the tissue-relevant oxygen level. The newest techniques for ex vivo expansion of HSPCs are based on data from the elucidation of the molecular mechanisms governing the hematopoietic niche function. Application of these methods has provided an improvement of several important clinical outcomes. Alternative methods of cord blood transplantation enhancement based on optimization of HPSC homing and engraftment in patient tissues have also been successful. The goal of the present review is to analyze recent methodological approaches to cord blood HSPC ex vivo amplification.

Circulating microRNAs.

The detection of miRNAs in plasma and other body fluids opened up a fascinating possibility that animal noncoding RNAs can act as extracellular signaling molecules. In this review, we discuss recent progress in the field including the ability of miRNAs to participate in intercellular communication in vitro and in vivo, and the application of circulating miRNAs as diagnostic markers of a wide range of diseases. Special attention is paid to the relevance of the development and unification of current techniques for isolation of circulating miRNAs.

Regulation of PGC-1α Isoform Expression in Skeletal Muscles.

The coactivator PGC-1α is the key regulator of mitochondrial biogenesis in skeletal muscle. Skeletal muscle expresses several PGC-1α isoforms. This review covers the functional role of PGC-1α isoforms and the regulation of their exercise-associated expression in skeletal muscle. The patterns of PGC-1α mRNA expression may markedly differ at rest and after muscle activity. Different signaling pathways are activated by different physiological stimuli, which regulate the expression of the PGC-1α gene from the canonical and alternative promoters: expression from a canonical (proximal) promoter is regulated by activation of the AMPK; expression from an alternative promoter, via a ß2-adrenergic receptor. All transcripts from both promoters are subject to alternative splicing. As a result, truncated isoforms that possess different properties are translated: truncated isoforms are more stable and predominantly activate angiogenesis, whereas full-length isoforms manly regulate mitochondrial biogenesis. The existence of several isoforms partially explains the broad-spectrum function of this protein and allows the organism to adapt to different physiological stimuli. Regulation of the PGC-1α gene expression by different signaling pathways provides ample opportunity for pharmacological influence on the expression of this gene. Those opportunities might be important for the treatment and prevention of various diseases, such as metabolic syndrome and diabetes mellitus. Elucidation of the regulatory mechanisms of the PGC-1α gene expression and their functional role may provide an opportunity to control the expression of different isoforms through exercise and/or pharmacological intervention.