Androgen Secretion Research Articles

Comparing Lean and Obese PCOS in Different PCOS Phenotypes: Evidence That the Body Weight Is More Important than the Rotterdam Phenotype in Influencing the Metabolic Status.

Polycystic Ovary Syndrome (PCOS) represents a heterogeneous disorder and, using Rotterdam diagnostic criteria, four main phenotypes (A, B, C, and D) have been distinguished. However, it remains unclear whether lean versus obesity status influences findings in the various phenotypes of women with PCOS. 274 women with PCOS were consecutively assessed. Among these women, there were 149 with phenotype A, 24 with phenotype B, 94 with phenotype C, and 7 with phenotype D. We found normal body weight to be very common (65%) in phenotype C patients, common (43%) in phenotype A and D patients, and less represented (but still 25%) in phenotype B patients. Obesity was common in phenotype B (54%) and phenotype A (33%) patients and uncommon in phenotype C (only 11%) and phenotype D (14%) patients. Obese and lean patients of each phenotype were compared. Compared to the phenotype C PCOS patients, both phenotype A and B patients had higher total testosterone circulating values and higher luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (p < 0.01) while anti-Mullerian hormone (AMH) levels were higher only in phenotype A PCOS patients. Instead, in the three obese PCOS phenotypes no differences in serum insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) calculation, and lipid blood values were observed. Analysis of data of lean patients gave similar results. Compared to the phenotype C PCOS patients, both phenotype A and B patients had higher total testosterone circulating values and higher LH/FSH ratio (p < 0.01) while AMH levels were higher only in phenotype A PCOS patients. However, no differences were observed in the circulating insulin levels, HOMA-IR calculation, or blood lipids between the three groups of lean PCOS patients. We conclude that Rotterdam phenotypes express the differences between PCOS patients in terms of ovulatory pattern and androgen secretion but fail to differentiate between obese patients with altered metabolic patterns and lean patients with normal metabolic patterns. A new classification of PCOS patients is needed and it should consider the influence of body weight on the metabolic patterns of PCOS patients.

Prenatal androgen treatment impairs the suprachiasmatic nucleus arginine-vasopressin to kisspeptin neuron circuit in female mice.

Polycystic ovary syndrome (PCOS) is associated with elevated androgen and luteinizing hormone (LH) secretion and with oligo/anovulation. Evidence indicates that elevated androgens impair sex steroid hormone feedback regulation of pulsatile LH secretion. Hyperandrogenemia in PCOS may also disrupt the preovulatory LH surge. The mechanisms through which this might occur, however, are not fully understood. Kisspeptin (KISS1) neurons of the rostral periventricular area of the third ventricle (RP3V) convey hormonal cues to gonadotropin-releasing hormone (GnRH) neurons. In rodents, the preovulatory surge is triggered by these hormonal cues and coincident timing signals from the central circadian clock in the suprachiasmatic nucleus (SCN). Timing signals are relayed to GnRH neurons, in part, via projections from SCN arginine-vasopressin (AVP) neurons to RP3VKISS1 neurons. Because rodent SCN cells express androgen receptors (AR), we hypothesized that these circuits are impaired by elevated androgens in a mouse model of PCOS. In prenatally androgen-treated (PNA) female mice, SCN Ar expression was significantly increased compared to that found in prenatally vehicle-treated mice. A similar trend was seen in the number of Avp-positive SCN cells expressing Ar. In the RP3V, the number of kisspeptin neurons was preserved. Anterograde tract-tracing, however, revealed reduced SCNAVP neuron projections to the RP3V and a significantly lower proportion of RP3VKISS1 neurons with close appositions from SCNAVP fibers. Functional assessments showed, on the other hand, that RP3VKISS1 neuron responses to AVP were maintained in PNA mice. These findings indicate that PNA changes some of the neural circuits that regulate the preovulatory surge. These impairments might contribute to ovulatory dysfunction in PNA mice modeling PCOS.

Oral exposure to DEHP may stimulate prostatic hyperplasia associated with upregulation of COX-2 and L-PGDS expressions in male adult rats

Di-(2-ethylhexyl) phthalate (DEHP), a typical environmental endocrine disruptor (EED), can disrupt estrogen and androgen secretion and metabolism process, thus inducing dysfunctional reproduction such as impaired gonadal development and spermatogenesis disorder. Prostaglandin synthases (PGS) catalyze various prostaglandins biosynthesis, involved in inflammatory cascade and tumorigenesis. Yet, little is known about how PGS may impact prostatic hyperplasia development and progression. This study concentrates predominantly on the potential prostatic toxicity of DEHP exposure and the mediating role of PGS. In vivo study, adult male rats were administered via oral gavage 30 μg/kg/d, 90 μg/kg/d, 270 μg/kg/d, 810 μg/kg/d DEHP or vehicle for four weeks. The results elucidated that low-dose DEHP may cause the proliferation of the prostate with an increased PCNA/TUNEL ratio. Given the importance of estrogens and androgens in prostatic hyperplasia, our first objective was to evaluate the levels of sex hormones. DEHP improved the ratio of estradiol (E2)/testosterone (T) in a dose-dependent manner and upregulated estrogen receptor alpha (ERα) and androgen receptor (AR) expressions. Prostaglandin synthases, including cyclooxygenase-2 (COX-2) and lipocalin-type prostaglandin D synthase (L-PGDS), were significantly upregulated in the ventral prostate. COX-2 and L-PGDS might mediate the tendency of prostatic hyperplasia induced by low-dose DEHP through estradiol/androgen regulation and imbalance between proliferation and apoptosis in vivo. These findings provide the first evidence that prostaglandin synthases contribute to the tendency toward benign prostatic hyperplasia induced by DEHP. Further investigations will have to be performed to facilitate an improved understanding of the role of prostaglandin synthases in DEHP-induced prostatic lesions.

A Review on Traditional and Modern Therapy in Management of Poly Cystic Ovarian Syndrome

Diet and lifestyle of an individual play a major role in maintaining the health of an individual, and any variation associated with these two factors would lead to serious consequences. Polycystic ovarian syndrome is one such condition which is an endocrine disorder observed in teen aged and premenopausal women in modern world, where there is formation of cysts on the ovary/ ovaries. It may be due to increased secretion of androgen, imbalance in doshas (vata, pitta and kapha), improper diet and lifestyle. There are various medicated and non-medicated therapies available for reducing the symptoms and conditions associated with poly cystic ovarian syndrome. Medicated treatment involves maintenance of hormonal balance, Type II diabetes mellitus, infertility, synchronisation of the vata, pitta and kapha, insulin resistance, regularization of menstrual cycle, reduction of acne and hirsutism and these are done by administration of allopathic and herbal formulations. Non-medicated treatment includes surgery by which cysts are removed and also by acceptance of healthy lifestyle. This review centres on providing information regarding the medicated and non-medicated treatment available for treating the type of conditions and symptoms consorted with poly cystic ovarian syndrome along with their pros and cons.

Heat stress and hypoxia inhibit the secretion of androgens and induce epithelial-to-mesenchymal transition associated with activated TGF-β/Smad signalling in canine cryptorchidism.

Cryptorchidism, as a common congenital disease of canine testes, is mainly caused by factors leading to endocrine abnormalities in testes and infertility in a heat stress and hypoxia microenvironment. Moreover, heat stress and hypoxia, as critical microenvironmental factors, promote epithelial-mesenchymal transition (EMT), which occurs during adult tissue remodelling responses including carcinogenesis and fibrosis and is the main cause of testicular tumours. In this study, we found by haematoxylin-eosin staining that the canine cryptorchid tissue produced a lot of collagen fibres. Also, the quantitative PCR and Western blot results showed that the mRNA and protein levels of the heat stress makers HSP70 and HO-1 and the hypoxia maker HIF-1α are significant higher compared with normal testes. Moreover, we found the expression levels of TGF-βs and its two receptors TGF-βRI and TGF-βRII increased in case of cryptorchidism. From the study in vitro, we found both heat stress and COCl2 mimic hypoxia inhibited the secretion of testosterone (T) and androstenedione (A4) and promoted the expression of the EMT maker α-SMA and vimentin in Leydig cells, and also that heat stress and COCl2 stimulated with the TGF-β signalling promoted the expression of TGF-βs and its two type receptors and also the active phosphorylation of Smad2 and Smad3. The use of LY2109761, a receptor inhibitor of TGF-βs/Smad signalling pathway, was associated with heat stress and COCl2 suppression of androgens' secretion and stimulated EMT in Leydig cells. These findings characterized a novel pathogenesis of cryptorchidism and provided a new idea for therapeutics.

Abstract 5281: Increased androgen secreted levels promote anti-proliferative effects on triple negative breast cancer

Abstract Endocrine therapies present poor effectivity in triple negative breast cancer (TNBC) but the reason is still unknown. However, in vitro experiments suggested that these therapies could be beneficial for inflammatory breast cancer, the most aggressive type of breast cancer. For this reason, the aim of this study is to determine why these therapies had poor effectiveness on TNBC. To this purpose, we evaluated the efficacy of Dutasteride (a 5α-Reductase inhibitor) and Anastrozole (an aromatase inhibitor) in three TNBC cell lines, SUM-149, SUM-159 and MDA-MD-231; and another no TNBC cell line, MCF-7. Sensitivity, proliferation and hormone secretion of estrone sulfate (E1SO4), estradiol (E2), testosterone (T) and dehydrotestosterone (DHT) was performed. Firstly, it was realized a sensitivity assay for determinate the half-maximal effective concentration (EC-50) of the two compounds in vitro. The results obtained from this aasay revealed an effective concentration of 1μM for each compound. Then, a cell proliferation assay was performed. Cells were seeded in 96-well plates with 1μM concentration of Dutasteride and Anastrozole for 24h. After, media was collected in order to determine hormone secretion of E1SO4, E2, T and DHT by an amplified enzymeimmunoassay. Our results revealed a significant reduction of 50% approximately in the TNBC cell lines for both treatments, except in MDA-231, which was more resistant, decreasing its proliferation in approximately 20%. However, the MCF-7 cell line had increased around 20% its proliferation. Regarding hormonal secretion, Dutasteride and Anastrozole treatments promoted a significant increase in T and DHT levels in TNBC cell lines while in MCF-7 a significant decreased was observed. Therefore, the increased on androgen secretion is related with the anti-proliferative effects of Dutasteride and Anastrozole in TNBC cell lines. However, both treatments also resulted in an increased on E1SO4 and E2 levels in all cell lines, being this increase greater in MCF-7. Therefore, although endocrine therapies could be effective in in vitro conditions, cells would be able to secret estrogens in order to survive and proliferate and limiting the effectiveness of these treatments. In conclusion, dutasteride and anstrozole promote a reduction in cell proliferation by increasing the secreted levels of androgens. The combination of these treatments with potent inhibitors of estrogen secretion may result in a promising treatment for TNBC. Citation Format: Sara Caceres, Belen Crespo, Angela Alonso-Diez, Gema Silvan, Josefina M. Illera, Alejandro Pascual, Maria J. Herrera, Miriam De La Puente, Juan Carlos Illera. Increased androgen secreted levels promote anti-proliferative effects on triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5281.

Emerging treatment for congenital adrenal hyperplasia.

Although the basic treatment of congenital adrenal hyperplasia (CAH) is well established, there are active clinical research projects to more closely mimic the normal diurnal rhythm of cortisol secretion and to reduce total glucocorticoid doses to minimize adverse metabolic effects. We review clinical studies on CAH treatment published in the last 18 months or currently underway according to ClinicalTrials.gov listings. These can be grouped into several broad themes: alternative dosing forms of hydrocortisone with altered pharmacokinetics or easier dose titration; corticotropin-releasing hormone receptor antagonists that reduce corticotropin (ACTH) secretion and thereby reduce adrenal androgen secretion; androgen biosynthesis inhibitors; a first clinical trial of a gene therapy vector. Alternative dosing forms of hydrocortisone are, or will shortly be, marketed, but cost may be a barrier to utilization, at least in the US market. Trials of corticotropin releasing hormone receptor antagonists and androgen biosynthesis inhibitors are currently underway. The author believes that trials of gene therapy for CAH are premature.

Concomitant dysregulation of androgen secretion and dysfunction of adipose tissue induced insulin resistance.

Hyperandrogenism and hyperinsulinemia have resulted from dysfunction of the theca cell of the ovary and adipose tissue and each one potentiates the other in patients with androgen excess disorders e.g., polycystic ovary disease and idiopathic hirsutism. Possible external and/or internal triggers can produce such cellular dysfunction. There is evidence that sodium valproate acts as a trigger of cellular dysfunction and produces both hyperinsulinemia and hyperandrogenism. Therefore, the elimination of these triggers can help the patients to recover from hyperinsulinemia, insulin resistance and hyperandrogenism.

Glucocorticoids and androgen secreting adrenocortical adenoma: A case report and literature review

Glucocorticoids and androgen secreting adrenocortical adenoma: A case report and literature review

Impaired steroid hormone feedback in polycystic ovary syndrome: Evidence from preclinical models for abnormalities within central circuits controlling fertility.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy and cause of infertility in women of reproductive age worldwide. Despite diagnostic features of anovulation, polycystic ovarian morphology, and high androgen secretion indicating the syndrome are the result of ovarian dysfunction, alterations to central neuroendocrine circuits that control reproductive capacity may drive PCOS symptoms. Resistance of gonadotrophin-releasing hormone (GnRH) neurons in the hypothalamus to inhibition by sex steroid hormone-negative feedback leads to a rapid frequency of pulsatile gonadotrophin secretion, which, in turn, drives the ovarian features of the disease. As GnRH neurons do not express steroid hormone receptors, impaired negative feedback is hypothesized to occur within an upstream network that controls GnRH pulse generation. This review will discuss the latest work from preclinical animal models of PCOS used to dissect the specific central mechanisms involved in impaired steroid hormone feedback. In particular, this review will focus on research that indicates neurons in the arcuate nucleus of the hypothalamus that express Kisspeptin, Neurokinin B and Dynorphin (KNDy cells) or γ-aminobutyric acid are targets of androgen-mediated impairment of steroid hormone feedback. Finally, this review will explore the development of therapeutic agents targeting neurons that control LH pulse frequency to resolve PCOS symptoms in the clinic.

Diagnostic Evaluation of Polycystic Ovarian Disease

Background: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects about one in 15 females worldwide. The major endocrine disruption is excessive androgen secretion or activity, and a large proportion of women also have abnormal insulin activity. Many body systems are affected, resulting in several health complications, including menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. Several biochemical tests play an important role in diagnosing and predicting health consequences of this disease. Aims: To determine the signs and symptoms of polycystic ovarian syndrome in gynaecology outpatient department of Jinnah Hospital Lahore and to describe the clinical presentations, biochemical findings and ultrasound findings in patients with polycystic ovarian syndrome. Design Descriptive case series Setting: Department of Obstetrics &amp; Gynecology, Jinnah Hospital Lahore from 1st March 2018 to 28th February 2019. Methodology: One hundred patients of reproductive age group with signs and symptoms of polycystic ovarian syndrome were included. A detailed history and examination was carried out. Then diagnosis of polycystic ovarian syndrome was confirmed by laboratory tests and ultrasound findings. Results: 72% patients presented with menstrual irregularities.56% patients had BMI&gt; 25kg/m2 .72% patients had hirsutism. Out of total patients 62% patients were married and 38% were unmarried. Among those who were married 24(38.7%) patients presented with primary infertility and 17(27.4%) presented with secondary infertility.44% patients had raised total serum testosterone. Diabetes mellitus was present in 14% of patients. Ultrasound criteria were fulfilled in 77% patients with polycystic ovarian disease. Conclusion: Most common clinical presentations of polycystic ovarian disease were found to be menstrual irregularities, hirsutism and obesity. Hyperinsulinemia and hyperandrogenism was also more commonly found in obese XIV and hirsute women. Also ultrasound is a very useful diagnostic tool for polycystic ovarian disease. Keywords: Polycystic ovarian disease, diagnostic evaluation, health consequences, diabetes mellitus, insulin resistance.

Clinical Study of Prevalence of Polycystic Ovarian Syndrome in Adolescent Girls with Irregular Menstruation

Background: Polycystic Ovarian Syndrome (PCOS) accounts for significant healthcare costs, emotional distress and significant impact on quality of life of women. Even though a fairly common problem it is a complex trait with unclear etiology. The present study was conducted to study various clinical presentations in the adolescent girls with polycystic ovarian syndrome having menstrual irregularities. Aims and Objectives: To study the anthropometric measurements among PCOS patients and to find the association of various risk factors. Material and Methods: It was an observational, cross-sectional study conducted in Out-patient department of Obstetrics and Gynecology at a tertiary healthcare center in Maharashtra. This study was conducted amongst the adolescent girls coming to the OPD of Obstetrics and Gynecology with irregular menses. Results: We evaluated the study subjects according to the Rotterdam’s criteria. We observed that 51.96% cases fulfilled two of the three criteria, while 29.13% cases fulfilled all the three criteria from Rotterdam’s criteria for PCOS. Oligomenorrhea was noted among 46.45% subjects, followed by hypomenorrhea among 32.28% cases. Primary amenorrhea was observed among 21.25% cases. Secondary amenorrhea was seen as the presenting symptom in 4.72% cases. Conclusions: Adolescents who had irregular menses and signs of increased androgen secretion should undergo investigations and must be treated. Prompt treatment following early diagnosis of PCOS helps improve quality of life in young adolescent girls.

ADVANCES IN RADIOTHERAPY OF ADRENAL GLAND LESIONS.

Primary adrenal tumors include a broad variety of lesions, from nonfunctioning incidentalomas to secreting adrenocortical adenomas including Aldosteronism, Cushing or androgen secreting lesions. Primary tumors can occur either in the cortex or the medulla of the adrenal glands, having different histopathological features and also different clinical appearances and treatment approaches. In addition, the adrenal glands can become distant metastatic sites of numerous primary malignancies. The first line of treatment in a broad variety of cases is surgery. After pathology results, in selected cases, apart the oncologic approach, radiotherapy could be an important therapeutic tool. In this paper we will discuss the role of radiotherapy in the treatment of adrenal gland lesions.

Prevalence of Hypothyroidism in PCOS in Jharkhand

Polycystic ovarian syndrome and thyroid disorders are common endocrine disorders in females worldwide. These two problems are having many common features but are with very different etiopathogenesis. The increase in ovarian volume and cystic changes in ovaries have been reported in primary hypothyroidism due to disturbed ratio of FSH and LH. It is also seen that thyroid disorders are more common in women with PCOS as compared to the normal population may be due to other associated factors like insulin resistance, increased androgen secretion and obesity. There might be some common factors in individuals predisposing to both disorders but till date not any common pathophysiology is established between these two. The increased ovarian volume and fertility improves by administration of thyroxin apart from that it helps to control obesity and to some extent obesity related disorders. The diagnosis of hypothyroidism during adolescence will be helpful to improve especially fertility and PCOS related clinical conditions. The thyroid function study was done in PCOS patients between 18 to 35 years of age residing in Jharkhand and the results were compared with age matched healthy women. Having no medical problem or on contraceptive steroids females. Serum fasting free t3,free t4 and TSH levels were estimated. PCOS was confirmed by USG. Results of present study shows the prevalence of hypothyroidism in PCOS patient in Jharkhand.

Effect of androgens on Sertoli cell maturation in human testis from birth to puberty

BackgroundAndrogens are well known to be necessary for spermatogenesis. The purpose of this study was to determine Sertoli cell responsiveness to androgens according to age from birth to puberty.ResultsTesticular tissue samples were studied in a population of 84 control boys classified into seven groups according to age: group 1 (1–30 days), group 2 (1–3 months), group 3 (3–6 months), group 4 (0.5–3 years), group 5 (3–6 years), group 6 (6–12 years), and group 7 (12–16 years). We compared these data with those of 2 situations of pathology linked to androgens: 1/premature secretion of testosterone: 4 cases of Leydig cell tumor (LCT) in childhood; and 2 /defect of androgen receptors (AR): 4 cases of complete form of insensitivity to androgen syndrome (CAIS). In control boys, AR immunoreactivity (ir) in Sertoli cells appeared between 4.6 and 10.8 years of age, Anti-Mullerian Hormone (AMH) ir in Sertoli cells disappeared between 9.2 and 10.2 years of age. Connexin 43 (Cx43) ir in Sertoli cells and histological features of the onset of spermatogenesis appeared between 10.8 and 13,8 years of age. Cx43 ir was significantly higher in 12–16 year-olds than in younger boys. In case of CAIS, no spermatogenesis was observed, both AR and Cx43 ir were undetectable and AMH ir was elevated in Sertoli cells even at pubertal age. In the vicinity of LCTs, spermatogenesis occurred and both AR and Cx43 ir were strongly positive and AMH ir in Sertoli cells was low for age.ConclusionsAndrogen action on Sertoli cells is required for onset of spermatogenesis and premature androgen secretion by LCT can induce spermatogenesis in the vicinity of the tumor. AR ir appeared earlier than onset of spermatogenesis, with large interindividual variability. The timing and mechanisms of Sertoli cell responsiveness to androgens are important issues for understanding the induction of spermatogenesis at puberty.

Androgen plays an important role in regulating the synthesis of pheromone in the scent gland of muskrat

The scent (musk) gland is an organ unique to muskrats and other scent-secreting animals, and the pheromones (musk) synthesized and secreted by the scent gland play a role in chemical communication among scent-secreting animals. The musk gland is synchronized with testicular developmental changes; however, little is known regarding androgen secretion from the testis and how this regulates pheromone synthesis and the secretion of scent. To investigate the effect of androgens on the synthesis of pheromones in the musk gland, we established a muskrat castration model by surgical removal of the testis, and analyzed the histomorphology, hormone concentration, gene expression, and changes in the chemical composition of the musk gland in castration and control groups by histomorphological analysis, Enzyme-Linked ImmunoSorbent Assay (ELISA), RNA sequencing (RNA-seq), and gas chromatography–mass spectrometry (GCMS). Histomorphological analysis results showed that after castration, muskrat gland cells underwent significant atrophy (P < 0.05). Hormone measurement results showed that there was a significant decrease in serum testosterone and muskrat musk testosterone (P < 0.05) after muskrat castration. Transcriptome sequencing results showed that 510 differentially expressed transcripts (DETs) were mainly enriched in fatty acid metabolism, terpenoid backbone biosynthesis, fatty acid degradation, PPAR signaling pathway, and fatty acid biosynthesis. GCMS results showed that macrocyclic ketones, steroids, fatty acids, alcohols, and esters in musk were significantly changed (P < 0.05). In conclusion, androgens were found to play an important function in the chemical communication exchange between muskrats through regulating pheromone synthesis in musk cells. This study provides a basis for understanding the mechanism of animal communication influenced by androgens.

Genome-Wide Association Study and Polygenic Risk Scores of Serum DHEAS Levels in a Chilean Children Cohort.

Adrenarche reflects the developmental growth of the adrenal zona reticularis, which produces increasing adrenal androgen secretion (eg, dehydroepiandrosterone [DHEA]/dehydroepiandrosterone sulfate [DHEAS]) from approximately age 5 to 15 years. We hypothesized that the study of the genetic determinants associated with variations in serum DHEAS during adrenarche might detect genetic variants influencing the rate or timing of this process. Genome-wide genotyping was performed in participants of the Chilean pediatric Growth and Obesity Chilean Cohort Study (GOCS) cohort (n = 788). We evaluated the genetic determinants of DHEAS levels at the genome-wide level and in targeted genes associated with steroidogenesis. To corroborate our findings, we evaluated a polygenic risk score (PRS) for age at pubarche, based on the discovered variants, in children from the same cohort. We identified one significant variant at the genome-wide level in the full cohort, close to the GALR1 gene (P = 3.81 × 10-8). In addition, variants suggestive of association (P < 1 × 10-5) were observed in PRLR, PITX1, PTPRD, NR1H4, and BCL11B. Stratifying by sex, we found variants suggestive of association in SERBP1 and CAMTA1/VAMP3 for boys and near ZNF98, TRPC6, and SULT2A1 for girls. We also found significant reductions in age at pubarche in those children with higher PRS for greater DHEAS based on these newly identified variants. Our results disclose one variant associated with DHEAS concentrations at the level of genome-wide association study significance, and several variants with a suggestive association that may be involved in the genetic regulation of adrenarche.

PREDICTORS AND PREMORBID CONDITIONS OF THE DEVELOPMENT OF FEMALE GENITAL CANCER, IN PARTICULAR ENDOMETRY CANCER AND BREAST CANCER

Objective: to review a new potential diagnostic criteria for predictors and premorbid conditions of female genital cancer, including endometrial cancer and breast cancer.&#x0D; Materials and methods. Bibliographic, information-analytical methods were used in the work. Sources of information were data from the scientific literature on the topic of the study, modern gadleins, a review of randomized controlled trials.&#x0D; Results. The results of epidemiological studies suggest that the increased risk of cancer of the female reproductive system is the presence of obesity and type 2 diabetes. Potential mechanisms of their association are hyperinsulinemia, hyperglycemia, chronic inflammation, and insulin resistance. Because insulin is a major regulator of cell metabolism and is a tissue growth factor, hyperinsulinemia increases the risk of cancer. Hyperinsulinemia is associated with increased secretion of androgens by the ovaries and decreased levels of the protein that binds sex hormones, leading to higher concentrations of biologically active estrogens, which are also known to be risk factors for female genital cancer. In recent years, PFAA profiles have been found to be significantly altered in cancer and type 2 diabetes. Because cancer cells require certain amino acids to synthesize DNA, tumor growth factors, build new blood vessels, and duplicate all of their protein content, changes in PFAA profiles can be used as biomarkers of disease and different types of cancer at different stages.&#x0D; Conclusions. With the growing incidence of cancer, the issue of early diagnosis and detection of cancer in the pre-clinical stages remains relevant. Protein metabolism in cancer remains unclear and requires further research using a larger sample size. In addition, the biological mechanisms by which amino acids may contribute to the risk and progression of cancer or other premorbid conditions need to be elucidated. Determining the exact mechanism underlying changes in PFAA profiles has great potential for cancer diagnosis and treatment.

Premature Pubarche Secondary to Herbal Oil Exposure

Premature pubarche (PP) is characterized by the growth of pubic hair before the age of 8 years in girls and 9 years in boys. In 80 to 95% of cases, PP is related to premature adrenarche (PA) secondary to idiopathic premature secretion of adrenal androgens. Although prepubertal pubarche is considered a variant of normal development, pathological causes should be ruled out, prompting a search for a source of androgen. Although hyperandrogenemia may be endogenous or exogenous in origin, most persons with prepubertal pubarche have normal serum concentrations of sex steroids, and an underlying cause is not identified. In such cases, possible exposure to endocrine disruptors should be considered. We report a case of premature pubarche in a 9-month-old boy who developed isolated pubarche after exposure to an herbal oil containing multiple essential oils including lavender, clary sage, grapefruit and peppermint. Pubarche resolved shortly after the use of herbal oil was discontinued.

Врожденная дисфункция коры надпочечников, обусловленная дефицитом 11β-гидроксилазы: поздняя диагностика и смена пола у ребенка двух лет

11β-hydroxylase deficiency is a rare autosomal recessive disorder due to impaired steroidogenesis in the adrenal cortex caused by pathogenic mutations in the CYP11B1 gene. The main clinical manifestations are determined by a deficiency of cortisol, ACTH hyperproduction, excessive androgens secretion and the accumulation of 11-deoxycorticosterone, which leads to the development of arterial hypertension. In the diagnostic search, it is important to take into account the ethnicity of the patient, since the frequency of the disease and the prevalence of mutations differ between ethnic groups. The article presents a clinical case of 11β-hydroxylase deficiency as the result of compound heterozygous mutations in the CYP11B1 gene in a patient of Turkic origin. This case shows the clinical manifestations and the development of complications of 11β-hydroxylase deficiency, the stages of differential diagnosis of patients with 21-hydroxylase deficiency.