Luteinizing Hormone Receptor Expression Research Articles

Luteinizing hormone receptor expression in lymphoma is not affected by body weight, sex, immunophenotype, or tumor stage in gonadectomized dogs

Purpose of this investigation was to determine if luteinizing hormone receptor (LHR) expressionin canine lymphoma was affected by body weight, sex, immunophenotype (B cell, T cell) or tumor stage.Formalin-fixed, paraffin-embedded lymphoma tissue samples from spayed and neutered dogs (n = 40),representing multiple breeds and mixed breeds, were subjected to routine immunohistochemicaltechniques using a polyclonal LHR antibody. Percentage of cells positive for LHR and the stainingintensity (scored 0 - 3) were determined at 400 x magnification. Data were expressed as mean ± standarddeviation and significance was defined as p < 0.05. Differences between sex and tumor phenotype, bodyweight and tumor stage were compared. All tumor samples had cells positive for LHR. However,percentage of cells expressing LHR and its immunostaining intensity varied among individuals. Therewere no significant differences in percentage of LHR positive cells or staining intensity within sex orimmunophenotype. Additionally, there was no significant association between percentage of LHRpositive cells or staining intensity within body weight or tumor stage. We concluded that increased risk oflymphoma in spayed and neutered dogs was not related to body weight, sex, immunophenotype or tumorstage. However, it is possible that risk of lymphoma may be related to increased LHR activationfollowing gonadectomy.

Expression of Luteinizing Hormone-Releasing Hormone (LHRH) and Type-I LHRH Receptor in Transitional Cell Carcinoma Type of Human Bladder Cancer

Bladder cancer (BC) is the tenth most frequently detected cancer in both sexes. Type-I luteinizing hormone-releasing hormone (LHRH) receptor (LHRH-R-I) is expressed not only in the pituitary, but also in several types of cancer disease. There are few data about LHRH-R-I expression in human BC. This study aimed to investigate the expression of LHRH and LHRH-R-I in the transitional cell carcinoma (TCC) type of human BC. RNA was extracted from 24 human bladder tumor specimens and three BC cell lines. RT-PCR was performed to detect mRNA for LHRH and LHRH-R-I. The protein of LHRH-R-I was further studied by immunohistochemistry (IHC), ligand competition assay, and Western Blot. PCR products of LHRH were found in 19 of 24 (79%) specimens and mRNA of LHRH-R-I was detected in 20 of 24 specimens (83%). Positive immunostaining for LHRH-R-I with different expression intensity was found in all samples examined, showing negative correlation with TCC grade. Radioligand binding studies also showed the presence of specific LHRH-R-I and high affinity binding of LHRH analogs. The high incidence of LHRH-R in BC suggests that it could serve as a molecular target for therapy of human BC with cytotoxic LHRH analogs or modern powerful antagonistic analogs of LHRH.

Characterization of stem cells from human ovarian follicular fluid; a potential source of autologous stem cell for cell-based therapy.

Human ovarian follicular fluid (HOFF) contains proteins, extracellular matrixes necessary for growth and maturation of oocytes as well as granulosa cells. Epithelial cells and stem cells can be isolated from HOFF. However, information regarding stem cells derived from HOFF is still lacking. The objectives of the present study were to isolate, characterize, and differentiate cells derived from HOFF. HOFF was collected during the routine aspiration of oocytes in an assisted fertilization program and subjected to cell isolation, characterization, and in vitro culture. After 24h of culture, different cell morphologies including epithelial-like-, neural-like- and fibroblast-like cells were observed. Immunocytochemistry reveals the expression of pluripotent stem cell markers (OCT4, NANOG, SSEA4), epithelial marker (CK18), FSH- and LH-receptor. For in vitro culture, the isolated cells were continuously cultured in a growth medium; alpha MEM containing 10% FBS and epidermal growth factor (EGF). After 2weeks of in vitro culture, cells with fibroblast-like morphology dominantly grow in the culture vessels and resemble mesenchymal stem cells (MSCs). HOFF-derived cells exhibited MSC expression of CD44, CD73, CD90, CD105, CD146, and STRO-1, and were capable of differentiation into osteoblasts, chondrocytes, and adipocytes. After induction of neural differentiation, HOFF-derived cells formed spheroidal structures and expressed neural stem cell markers including Nestin, β-tubulin III, and O4. Besides, the oocyte-like structure was observed after prolonged culture of HOFF. In conclusion, cells derived from follicular fluidexhibited stem cell characteristics, which could be useful for regenerative medicine applications and cell-based therapies.

Assessment of Testicular Lhcgr mRNA Expression Correlated with Testis and Seminal Vesicle Activities in the Libyan jird (Meriones libycus, Rodentia: Muridae) during Breeding Season Compared with Nonbreeding Season.

Simple SummaryThe breeding periods of desert rodents should be favorable to the survival of small young, conditioned by the availability of food that occurs in the Libyan jird biotope during the long photoperiod and the high temperatures. The Libyan jird (Meriones libycus) were caught in their natural biotope in the Saharan desert in Algeria and showed a seasonal cycle of the testis activity, characterized by the highest peak during spring (the breeding season) and the lowest activity was registered during autumn and winter (nonbreeding season). Lhcgr mRNA expression is increased in autumn and decreased in spring. This expression varied in an opposite manner to testicular and seminal vesicle structures. The Libyan jird (Meriones libycus, 1823) is a wild desert rodent that is a seasonal breeder species adapted to breed when the environmental conditions can satisfy the energy and hydrous requirements of pregnant and nursing females to ensure that births occur at the most favorable time of the year. We assessed gene expression of testicular luteinizing hormone receptor (Lhcgr) correlated to testis activity. The expression of Lhcgr was evaluated using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR and the testis activity by a histological method in adult male Libyan jirds during the nonbreeding and breeding seasons. Our results showed that Lhcgr mRNA expression increased in autumn during the nonbreeding season and decreased in spring during the breeding season. This expression varied in contrast to testicular structure or function and plasma testosterone levels. These results help to elucidate this desert rodent’s seasonal sexual activity, which is correlated with central regulation.

Влияние низкомолекулярного аллостерического агониста рецептора лютеинизирующего гормона на функциональное состояние семенников у стареющих и диабетических крыс

Human chorionic gonadotropin that is widely used for improving spermatogenesis. The effect of chorionic gonadotropin is mediated through luteinizing hormone receptor. Treatment with gonadotropin is associated with undesirable effects due to hyperactivation of testosterone production and luteinizing hormone receptor desensitization. A promising alternative could be low-molecular-weight agonists of luteinizing hormone receptors, but their effects on spermatogenesis have not been investigated. Here we analyzed the effect of a thieno[2,3-d]pyrimidines (TP), 4-((3-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno [2,3-d]pyrimidine-4-yl) phenyl)carbamoyl)pyridine 1-oxide (TP22), an allosteric agonist of luteinizing hormone receptors, on the seminiferous tubules and spermatogenic cells in 4- and 18-month-old male rats and in animals with diabetes mellitus. TP22 and gonadotropin were administered in daily doses of 15 mg/kg and 20 U/rat for 5 days. Blood testosterone level, morphology of the seminiferous tubules, and the number of germ cells in them were estimated. Being comparable by the efficiency to gonadotropin, TP22 increased the testosterone level in all the studied groups of rats and restored epithelium thickness in the seminiferous tubules and the number of spermatogonia and pachytenic spermatocytes that are reduced in aging and diabetes, but, unlike gonadotropin, did not suppress the expression of luteinizing hormone receptor. The efficacy of TP22 as a stimulator of testicular spermatogenesis has been demonstrated both under normal conditions and in age-related and diabetes-associated reproductive dysfunctions.

ВЛИЯНИЕ НИЗКОМОЛЕКУЛЯРНЫХ АЛЛОСТЕРИЧЕСКИХ АГОНИСТОВ РЕЦЕПТОРА ЛЮТЕИНИЗИРУЮЩЕГО ГОРМОНА НА ЕГО ЭКСПРЕССИЮ В СЕМЕННИКАХ САМЦОВ КРЫС

Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) regulate testicular steroidogenesis by interacting with the orthosteric site located in the extracellular domain of the LH receptor (LHR). The use of hCG and LH in medicine is fraught with side effects caused by hyperactivation of LH-dependent cascades and the development of resistance of target cells to endogenous gonadotropins due to a decrease in the activity and expression of LHR. An alternative to gonadotropins is low-molecular-weight compounds which interact with the LHR transmembrane allosteric site. The aim of this work was to study the relationship between the steroidogenic effects of hCG and thieno[2,3-d]pyrimidine derivatives (TPDs) with an activity of LHR agonists and their ability to influence the expression of the LRH-encoding Lhr gene both in vitro, when acting on the primary culture of rat Leydig cells, and in vivo, when administered to male rats. hCG stimulated testosterone production with a high efficiency at an early stage of its effect on Leydig cells (after 30 min) and upon a single administration to male rats (after 3 h), exceeding TPDs in activity by this parameter. After 1–3 h of acting on Leydig cells and long-term administration to male rats, the steroidogenic effect of hCG decreased and became comparable to that of TPDs. In Leydig cells and rat testes, hCG suppressed Lhr gene expression, which was partially restored in vivo on days 7–10 being accompanied by a slight increase in the steroidogenic effect of hCG, though to a significantly smaller extent than on the first day. The treatment with TP03, which was the most active of the TPDs studied, had a little effect on Lhr gene expression in Leydig cells but significantly increased it in rat testes after long-term administration of the drug. The steroidogenic effect of TP03 positively correlated with Lhr gene expression. When TP03 was applied to aging rats, its steroidogenic effect decreased, most likely, due to the absence of its stimulating effect on LHR expression. Thus, after long-term administration, TPDs exert a moderately expressed, stable over time, stimulating effect on testosterone production but do not decrease LHR expression, which prevents testicular resistance to endogenous gonadotropins under conditions of steroidogenesis stimulation.

Adrenal cortex stimulation with hCG in spayed female dogs with Cushing's syndrome: Is the LH-dependent variant possible?

Background:The expression and overexpression of luteinizing hormone (LH) receptors in the canine adrenal gland cortex have been reported. Therefore, it was hypothesized that a LH-dependent form of Cushing’s syndrome (CS) could exist in dogs. Aim:To assess whether the adrenal gland post-ovariectomy (OVx) exhibits a greater response to adrenocorticotrophin (ACTH) stimulation; to evaluate whether the adrenal gland responds to human chorionic gonadotropin (hCG) stimulation by increasing the release of cortisol; and to consider whether hCG stimulus testing would be useful as a diagnosis for possible cases of LH-dependent CS.Methods:Cortisol concentrations were measured from healthy female dogs (n=16) at baseline and following ACTH stimulation before and 2 months after gonadectomy (OVx). Cortisol concentrations were also measured for female dogs with CS (n = 14) following administration of hCG (5000 IU). A post-hCG cortisol concentration greater than 140 nmol/l was used to define dogs with LH-dependent Cushing’s syndrome.Results:In normal female dogs, both pre- and post-stimulation cortisol concentrations increased following OVx (p = 0.002 and p = 0.0003, respectively). In female dogs with CS, cortisol concentrations increased following stimulation with hCG in 57% (8/14; p = 0.002). Age at the time of OVx was associated (p = 0.015) with the cortisol response to hCG [8 (5–9) years vs. 3.5 (2–6) years, p = 0.0013).Conclusion:Based on these results, an LH-dependent form of CS occurs in spayed female dogs, and that it is more likely to occur when female dogs are spayed later in life.

Relationship Between Uterine Development, mRNA and Protein Expression of FSH and LH Receptors in New Zealand White Rabbits

Relationship Between Uterine Development, mRNA and Protein Expression of FSH and LH Receptors in New Zealand White Rabbits

BMP2 increases the production of BDNF through the upregulation of proBDNF and furin expression in human granulosa-lutein cells.

Locally produced in human granulosa cells of the developing follicle, bone morphogenetic protein 2 (BMP2) plays a crucial role in the regulation of ovarian folliculogenesis and luteal formation. Brain-derived neurotrophic factor (BDNF) is an intraovarian neurotrophic factor that has been shown to promote oocyte maturation and subsequent fertilization competency. At present, little is known regarding the intracellular regulation, assembly and secretion of endogenous BDNF in human granulosa cells. The aim of this study was to explore the effect of BMP2 on the expression and production of BDNF in human granulosa cells and the molecular mechanisms underlying this effect. An immortalized human granulosa cell line (SVOG) and primary human granulosa-lutein (hGL) cells were utilized as in vitro study models. Our results showed that BMP2 significantly increased the mRNA and secreted levels of BDNF. Additionally, BMP2 upregulated the expression of furin at the transcriptional and translational levels. Knockdown of endogenous furin partially attenuated the BMP2-induced increase in BDNF production, indicating that furin is involved in the maturation process of BDNF. Using pharmacological (kinase receptor inhibitors) and siRNA-mediated inhibition approaches, we demonstrated that BMP2-induced upregulation of BDNF and furin expression is most likely mediated by the activin receptor-like kinase (ALK)2/ALK3-SMAD4 signaling pathway. Notably, analysis using clinical samples revealed that there was a positive correlation between follicular fluid concentrations of BMP2 and those of BDNF. These results indicate that BMP2 increases the production of mature BDNF by upregulating the precursor BDNF and promoting the proteolytic processing of mature BDNF. Finally, we also investigated the effects of BMP2 on ovarian steroidogenesis and the results showed that BMP2 treatment significantly increased the accumulated level of estradiol (by upregulating the expression of FSH receptor and cytochrome P450 aromatase), whereas it decreased the accumulated level of progesterone (by downregulating the expression of LH receptors and steroidogenic acute regulatory protein) in primary hGL cells. Our findings provide a novel paracrine mechanism underlying the regulation of an intraovarian growth factor in human granulosa cells.

Current concepts of polycystic ovary syndrome pathogenesis.

This review provides a model for understanding polycystic ovary syndrome (PCOS) pathophysiology and updates the evidence on which it is based. Then, it highlights complimentary molecular genetic and epigenetic advances in understanding PCOS cause. Important studies into PCOS cause built on the 2014 discovery of a novel regulatory protein variant that underlies the typical PCOS steroidogenic abnormalities: DENND1A.V2 (differentially expressed in normal and neoplastic development, isoform 1A, variant 2). Over 30 DENND1A gene variants have been found, the vast majority upstream of the coding sequence and potentially regulatory. These variants are individually uncommon but collectively plausibly cause 50% of PCOS. Anti-Müllerian hormone (AMH)/AMH receptor variants with decreased function possibly cause 6.7% of PCOS. DENNND1A was recently reported to belong to a signaling network that upregulates luteinizing hormone receptor expression and insulin mitogenic signaling. Prenatal androgen administration has proven to be a potent epigenetic regulator that causes transgenerational epigenomic changes in a mouse PCOS model with similarities to those in human PCOS and PCOS daughters. In addition to finding how gene variants contribute to PCOS pathogenesis, better understanding of androgen epigenetic mechanisms of action in diverse tissues can be expected to expand our understanding of PCOS pathogenesis.

Association between LH receptor regulation and ovarian hyperstimulation syndrome in a rodent model.

Ovarian hyperstimulation syndrome (OHSS) is a common complication of ovarian stimulation associated with the administration of human chorionic gonadotropin (hCG) during assisted reproduction. We have determined the expression of luteinizing hormone receptor (Lhcgr) mRNA, vascular endothelial growth factor (VEGF), and its transcription factor, HIF1α, during the periovulatory period in a rodent model of OHSS and compared these results with normal ovulatory periods. These results showed that the downregulation of Lhcgr mRNA in response to conditions that mimic preovulatory LH surge was significantly impaired in the OHSS group compared to the complete downregulation seen in the control group. Most importantly, the downregulation of luteinizing hormone receptor mRNA expression following hCG administration was sustained in the control group up to 48 h, whereas it remained at significantly higher levels in the OHSS group. This impairment of hCG-induced Lhcgr downregulation in the OHSS group was accompanied by significantly elevated levels of VEGF and its transcription factor, HIF1α. Furthermore, the downregulation of Lhcgr that occurs in response to a preovulatory LH surge in normal cycles was accompanied by low levels of VEGF. This study shows that, while downregulation of Lhcgr as well as low VEGF levels are seen in response to a preovulatory LH surge in normal ovarian cycle, impaired Lhcgr downregulation and elevated VEGF levels were found in the OHSS group.

Assessment of luteinizing hormone receptor expression in structural support tissues of canine hip and femorotibial joints.

To determine whether luteinizing hormone receptors (LHRs) are expressed in canine femoral head subchondral bone (FHSB), hip joint round ligament (RL), cranial cruciate ligament (CCL), and femorotibial joint synovium (FJS) specimens. 1 specimen each of the FHSB, RL, CCL, and FJS obtained from the left hind limbs of 19 fresh canine cadavers. 1 section of each FHSB, RL, CCL, and FJS specimen was processed with rabbit polyclonal IgG anti-human LHR antibody, and 1 section was treated with negative control reagents. Percentage immunoexpression of LHRs in FHSB and FJS sections was analyzed by assessment of 100 bone marrow cells or synoviocytes in 3 adjacent hpf (400×). In each RL and CCL section, immunoexpression of LHRs in fibrocytes was semiquantitatively analyzed on the basis of the mean of the product of percentage staining score (from 0 [no staining] to 3 [> 50% of cells stained]) and staining intensity score (from 0 [no staining] to 2 [moderate to strong staining]) for 3 adjacent hpf. All tissues examined had variable LHR expression. Expression of LHRs in FHSB, CCL, or FJS specimens did not differ between sexes or between sexually intact and gonadectomized dogs. However, RL specimens from female dogs had significantly greater LHR expression scores, compared with findings for male dogs. Results indicated that LHRs are expressed in structural support tissues of canine hip and femorotibial joints. Further research is required to determine the LHRs' function, mechanism of action, and potential contribution to the pathogenesis of hip dysplasia or CCL rupture in dogs.

SUN-161 Primary Aldosteronism and Klinefelter’s Syndrome: Two Cases

Background: Primary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of LH receptor in patients with PA has been reported, however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Clinical Cases: Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a two-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Conclusion: Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered.

Effects of Luteinizing Hormone Receptor Expression Level on Receptor Aggregation and Function

Effects of Luteinizing Hormone Receptor Expression Level on Receptor Aggregation and Function

Downregulation of testosterone production through luteinizing hormone receptor regulation in male rats exposed to 17\u03b1-ethynylestradiol

The pharmaceutical 17α-ethynylestradiol (EE2) is considered as an endocrine-disrupting chemical that interferes with male reproduction and hormonal activation. In this study, we investigated the molecular mechanism underlying EE2-regulatory testosterone release in vitro and in vivo. The results show that EE2 treatment decreased testosterone release from rat Leydig cells. Treatment of rats with EE2 reduced plasma testosterone levels and decreased the sensitivity of human chorionic gonadotropin (hCG). EE2 reduced luteinizing hormone receptor (LHR) expression associated with decreased cAMP generation by downregulation of adenylyl cyclase activity and decreased intracellular calcium-mediated pathways. The expression levels of StAR and P450scc were decreased in Leydig cells by treatment of rats with EE2 for 7 days. The sperm motility in the vas deferens and epididymis was reduced, but the histopathological features of the testis and the total sperm number of the vas deferens were not affected. Moreover, the serum dihydrotestosterone (DHT) level was decreased by treatment with EE2. The prostate gland and seminal vesicle atrophied significantly, and their expression level of 5α-reductase type II was reduced after EE2 exposure. Taken together, these results demonstrate an underlying mechanism of EE2 to downregulate testosterone production in Leydig cells, explaining the damaging effects of EE2 on male reproduction.

Impact of Serum Human Chorionic Gonadotropin and Luteinizing Hormone Receptor Expression to Oocyte Maturation Rate: A Study of Controlled Ovarian Stimulation.

Background:Few studies have assessed the impact of serum human chorionic gonadotropin (hCG) levels before oocyte retrieval and luteinizing hormone receptor (LHR) mRNA expression.Aims:The objective was to assess the correlations between serum hCG levels at 12-h posttrigger granulosa cell LHR mRNA expression during the in vitro fertilization (IVF) cycle with oocyte maturation rate and to determine the cutoff level of serum hCG at 12-h posttrigger.Settings and Design:A cross-sectional was conducted for this study at the IVF center of Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.Materials and Methods:Recombinant follicle-stimulating hormone was used on day 2 of the menstrual cycle with multiple doses of a gonadotropin-releasing hormone antagonist. Recombinant hCG was used to trigger ovulation. At 12-h posttrigger, hCG serum levels were measured using an enzyme-linked immunosorbent assay.Statistical Analysis:Pearson's correlation coefficient was used to evaluate the correlation between oocyte maturation rates, serum hCG levels, and LHR mRNA levels. Cutoff values were determined using a receiver operating characteristic (ROC) curve.Results:Serum hCG levels were positively correlated (r = 0.467;P < 0.01), and LHR mRNA expression was weakly correlated (r = 0.073; P = 0.701) with oocyte maturation. The cutoff of serum hCG for a high maturation rate was 77 mIU/mL, with an area under the ROC curve of 0.765 (95% confidence interval: 0.598–0.939) andP < 0.001.Conclusion:Oocyte maturation is correlated with serum hCG levels with 77 mIU/mL as the cutoff point for oocyte retrieval.

Gene Expression of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) Receptors in Some of the Reproductive Organs of Giant African Land Snail (Archachatina marginata)

The role of receptors in the exertion of the hormonal effect on their target cell creates a better understanding of the mechanism of action of hormones. In the snail, Archachatina marginata, there is a dearth of information on the gene expression of FSH and LH receptors. This experiment was conducted to determine the effects of exogenous administration of gonadotropin (PMSG) and some sex steroid hormones (Progesterone (P4) and 17β-Oestradiol (E2)) on the levels of gene expression of FSH and LH in some selected reproductive organs of Archachatina marginata. The experiment was laid out in 4x3x2 factorial design in Completely Randomised Design comprising of 432 snails randomly allotted to 24 treatment groups of 18 snails per group of Control, P4, E2 and PMSG at 3 dosage levels (Low-1 µg/ml, Medium-5 µg/ml and High-10 µg/ml for P4 and E2; and Low-1 IU/ml, Medium-10 IU/ml and High-20 IU/ml for PMSG) at 2 durations of injections (16-days of four injections and 32-days of eight injections). The gel viewed under the ultra-violet light source showed that the expression of LHR receptor did not appear in all the organs considered. However, FSHR receptor was noted in their appearance in the albumen gland, little hermaphrodite duct, common hermaphrodite duct and vagina of A. marginata. Administration of E2 of 5 µg/ml for 16 days and 32 days increase the gene expression of FSH receptors in the common hermaphrodite duct and vagina of A. marginata respectively. Also, injections of 5 µg/ml of P4 for 16 days gave a relative increase in the levels of expression of FSH receptors in the little hermaphrodite duct, while the highest level was on the albumen of snails injected with 1 µg/ml of E2 for 32-days of eight injections. Injection of 5 µl/ml of P4 for 16-days of four injections, 5 µl/ml of E2 for 32-days of eight injections, 5 µl/ml of E2 for 16-days of four injections, 1 µl/ml of E2 of 32-days of eight injections increased the gene expression of FSH in the little hermaphrodite duct, vagina, common hermaphrodite duct and albumen respectively. Therefore, it is informed here that administration of P4, E2 and PMSG exogenously to A. marginata of reproductive age induces an increase in the levels of gene expression of FSH receptors.

Primary aldosteronism in Klinefelter's syndrome: two cases.

SummaryPrimary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered.Learning points:The pathogenesis of primary aldosteronism is still unclear.Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma.Serum luteinizing hormone, which is increased in patients with Klinefelter’s syndrome, might contribute to the development of primary aldosteronism.

Expression of the luteinizing hormone receptor (LHR) in ovarian cancer

We investigated the association of LHR expression in epithelial ovarian cancer (OC) with clinical and pathologic characteristics of patients. LHR expression was examined immunohistochemically using tissue microarrays (TMAs) of specimens from 232 OC patients. Each sample was scored quantitatively evaluating LHR staining intensity (LHR-I) and percentage of LHR (LHR-P) staining cells in tumor cells examined. LHR-I was assessed as no staining (negative), weak (+ 1), moderate (+ 2), and strong positive (+ 3). LHR-P was measured as 1 to 5, 6 to 50% and > 50% of the tumor cells examined. Positive LHR staining was found in 202 (87%) patients’ tumor specimens and 66% patients had strong intensity LHR expression. In 197 (85%) of patients, LHR-P was measured in > 50% of tumor cells. LHR-I was significantly associated with pathologic stage (p = 0.007). We found that 72% of stage III or IV patients expressed strong LHR-I in tumor cells. There were 87% of Silberberg’s grade 2 or 3 patients compared to 70% of grade 1 patients with LHR expression observed in > 50% of tumor cells, p = 0.037. Tumor stage was significantly associated with overall survival and recurrence free survival, p < 0.001 for both analyses, even after adjustment for age, tumor grade and whether patient had persistent disease after therapy or not. Our study demonstrates that LHR is highly expressed in the majority of OC patients. Both LHR-I and LHR-P are significantly associated with either the pathologic stage or tumor grade.

Direct actions of gonadotropins beyond the reproductive system and their role in human aging and neoplasia [Bezpośrednie działanie gonadotropin poza układem rozrodczym i ich rola w starzeniu się i nowotworzeniu u człowieka

Pituitary hormones folitropin (follicle-stimulating hormone, FSH) and lutropin (luteinising hormone, LH) are known as the key regulators of human reproduction. However, their receptors have been identified also in several organs and tissues beyond the reproductive system, and there is cumulating evidence of their direct extra-gonadal actions. The expression of LH receptors (LHR) was found in the brain and adrenal cortex. FSH receptors (FSHR) were found to be expressed in osteoclasts, monocytes, adipocytes, and peri- and intra-tumoural blood vessel endothelia of malignant tumours. Other localisations of FSHR and LHR are also suggested by immunohistochemistry, but these findings need confirmation using molecular biology techniques. Because the high levels of gonadotropins are a constant phenomenon during human aging, especially in postmenopausal women, it is hypothesised that the direct actions of FSH and LH are involved in the pathogenesis of age-related disorders. The proposal of therapy based on the inhibition of gonadotropin hypersecretion is also discussed.