Higher Inhibin Research Articles

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study.

PurposeWe assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies.Materials and MethodsThis study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities.ResultsAmong 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36–5.13] and major CHDs (aOR 7.30; 95% CI 3.18–15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42–12.46) was associated with non-chromosomal major CHDs.ConclusionUltrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Live birth after in-vitro maturation of oocytes in a patient with specific ovarian insufficiency caused by long-term mitotane treatment for adrenocortical carcinoma

Research questionHow should the fertility of a woman with persistent specific ovarian dysfunction after long-term mitotane exposure be managed? DesignCase report. A 33-year-old woman who underwent surgery for adrenocortical carcinoma and treated with mitotane was referred for infertility. She rapidly became amenorrhoeic while taking mitotane, a condition that persisted for 5 years after cessation. Repeated serum hormone evaluation showed collapsed androgen levels, low oestradiol, high gonadotrophins (LH 69 and 63; FSH 23 and 43 IU/l), relatively high inhibin B level and slightly decreased anti-Müllerian hormone levels (1.4 and 0.7 ng/ml). An ultrasound scan revealed an antral follicle count of 13, contrasting with high serum gonadotrophin levels. After failure to obtain follicular growth after ovarian stimulation, in-vitro maturation (IVM) of immature oocytes aspirated from the antral follicles was carried out for microinjection with the spermatozoa of the patient's partner. ResultsTwo cycles of unstimulated egg retrieval were carried out, producing seven IVM oocytes, which were microinjected. A total of three cleavage-stage embryos were vitrified and unsuccessfully transferred after endometrial preparation using hormone replacement therapy (HRT). After a 20-month break, two new attempts were carried out under HRT with the aim of achieving a fresh embryo transfer. The last attempt succeeded after transfer of a single day-2 embryo, and the patient delivered a healthy baby. ConclusionPersistent specific impaired ovarian function 5 years after withdrawal of mitotane, and the first live birth after IVM in this situation, are reported. The question of fertility preservation before long-term mitotane treatment is raised.

Second trimester maternal serum biomarkers and the risk of cerebral palsy.

To investigate whether second trimester maternal serum screening (2TMSS) biomarkers are associated with cerebral palsy (CP) and identify CP characteristics associated with abnormal biomarker levels. In this retrospective case-control data linkage study, we linked mothers of 129 singleton CP cases from a population register to their 2TMSS records and selected 10 singleton pregnancy controls per case (n=1290). We compared mean and abnormal levels of alpha-fetoprotein (AFP), beta subunit of human chorionic gonadotrophin (β-hCG), unconjugated estriol (uE3), and inhibin between cases and controls and within CP subgroups. Compared to control pregnancies, CP pregnancies had higher mean levels of AFP (1.10 vs. 1.01 multiple of the population median [MoM], p=0.01) and inhibin (1.10 vs. 0.98 MoM, p≤0.01). CP pregnancies were 2.5 times more likely to be associated with high levels of AFP (OR 2.52 [95% confidence interval [CI] 1.30, 4.65]; p<0.01) and 2.6 times for inhibin (OR 2.63 [95% CI 1.37, 4.77]; p<0.01), and 6.8 times when AFP and inhibin were both elevated (OR 6.75 [95% CI 2.41, 18.94]; p<0.01). In CP cases, high AFP and high inhibin levels were associated with preterm birth and low birthweight. Abnormal second-trimester biomarker levels suggest abnormal placentation plays a role in the causal pathway of some CP cases.

Serum and intratesticular inhibin B, AMH, and spermatogonial numbers in trans women at gender-confirming surgery: An observational study.

Anti-Müllerian hormone and inhibin B are produced by Sertoli cells. Anti-Müllerian hormone secretion indicates an immature Sertoli cell state. Inhibin B serves as a marker of male fertility. Identification of markers reflecting the presence of germ cells is of particular relevance in trans persons undergoing gender-affirming hormone therapy in order to offer individualized fertility preservation methods. Serum and intratesticular inhibin B and anti-Müllerian hormone values were assessed and related to clinical features, laboratory values, and germ cell numbers. Twenty-two trans women from three clinics were included. As gender-affirming hormone therapy, 10-12.5mg of cyproterone acetate plus estrogens were administered. Height, weight, age, medication, and treatment duration were inquired by questionnaires. Serum luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol were measured by immuno-assays. Serum and intratesticular inhibin B and anti-Müllerian hormone were measured by commercially available ELISAs. Spermatogonia were quantified as spermatogonia per cubic millimeter testicular tissue applying a morphometric analysis of two independent testicular cross-sections per individual after MAGEA4 immunostaining. Patients with high inhibin B levels presented with a higher number of spermatogonia (*p<0.05). Furthermore, mean serum inhibin B was associated with low age (*p<0.05), low follicle-stimulating hormone (*p<0.05), and low testosterone (*p<0.05). Serum anti-Müllerian hormone, however, was not related to spermatogonial numbers. It correlated with high testosterone (*p<0.05) and high follicle-stimulating hormone (*p<0.05) only. High intratesticular inhibin B was accompanied by high luteinizing hormone (*p<0.05), high follicle-stimulating hormone (**p<0.01), and high testosterone levels (**p<0.01). Higher the intratesticular anti-Müllerian hormone levels, the longer gender-affirming hormone therapy was administered (*p<0.05). Serum inhibin B levels indicate the presence of spermatogonia, whereas anti-Müllerian hormone seems not to be a reliable marker concerning germ cell abundance.

Serum markers in quadruple screening associated with adverse pregnancy outcomes: A case–control study in China

BackgroundWe assessed whether the results of quadruple screening during pregnancy are associated with an increased risk of adverse pregnancy outcomes. MethodsWe measured serum marker concentrations using quadruple screening in the second trimester of pregnancy and analyzed the relationship between adverse perinatal outcomes and serum markers in 12,124 pregnant women. A multivariate logistic regression analysis was used to evaluate the relative risk of quadruple screening and adverse pregnancy outcomes. ResultsCompared with the control group, increased concentrations of alpha-fetoprotein (AFP) and inhibin A were risk factors for preeclampsia and preterm delivery; low concentrations of unconjugated estriol and high inhibin A were risk factors for pregnancy hypertension; an increased concentration of human chorionic gonadotropin (hCG) was a risk factor for gestational diabetes mellitus; high AFP, low hCG, and high inhibin A were risk factors for low birth weight; and low AFP and high hCG were risk factors for macrosomia. ConclusionsQuadruple screening in the second trimester of pregnancy can provide early warning signs for maternal and fetal adverse pregnancy outcomes.

Testicular function in boys with 47,XYY and relationship to phenotype.

An additional Y chromosome occurs in ~1 in 1,000 males, resulting in the karyotype 47,XYY. The phenotype includes tall stature, hypotonia, neuropsychiatric comorbidities, and an increased risk of infertility in adulthood. Little is known about testicular function in childhood and adolescence in 47,XYY. This cross-sectional study aimed to assess testicular function serum biomarkers, including total testosterone, inhibin B, and anti-mullerian hormone (AMH), in 82 boys with XYY (11.3 ± 3.8 years) compared with 66 male controls (11.6 ± 3.8 years). The association of testicular hormones with physical features, neuropsychological phenotype, and magnetoencephalography (MEG) was assessed with multiple linear regression models. Results indicate males with XYY have significantly lower inhibin B (median 84 pg/ml vs. 109 pg/ml, p = .004) and higher AMH (median 41 ng/ml vs. 29 ng/ml, p = .011); however, testosterone, testicular volume, and stretched penile length were not different from controls. In the exploratory analysis of relationships between hormone concentrations and phenotypic assessments, higher inhibin B concentrations were positively correlated with lower BMI and better cognitive, academic, and behavioral outcomes in the XYY group. Testosterone concentrations were positively associated with better behavioral outcomes in boys with XYY. Higher testosterone and inhibin B concentrations were also associated with shorter auditory latencies measured using magnetoencephalography (MEG) in XYY. With a few exceptions, testicular hormones were not associated with phenotypic outcomes in controls. In conclusion, there is evidence of subtle impaired testicular function in boys with XYY and a newly described relationship between measures of testicular function and some aspects of the XYY phenotype.

Possible involvement of the glucocorticoid receptor (NR3C1) and selected NR3C1 gene variants in regulation of human testicular function.

Perceived stress has been associated with decreased semen quality but the mechanisms have not been elucidated. It is not known whether cortisol, the major stress hormone in humans, can act directly via receptors in the testis, and whether variants in the gene encoding the glucocorticoid receptor (NR3C1) can possibly modulate the effect. To address these questions, we investigated the expression of the glucocorticoid receptor in human testicular tissue, including adult and fetal samples (n=20) by immunohistochemical staining, and in silico analysis of publicly available datasets. In the adult testis NR3C1 protein was detected in peritubular cells, a subset of Leydig cells, Sertoli cells (weak), and spermatogonia, but not in spermatids. The NR3C1 expression pattern in fetal testis samples differed by a notably stronger reaction in Sertoli cells, lack of staining in gonocytes but the presence in a subset of pro-spermatogonia, and the almost absent reaction in nascent peritubular cells. In parallel, we explored the association between adult testicular function and three single nucleotide NR3C1 polymorphisms (BcII [rs41423247], 9β [rs6198], and Tth111I [rs10052957]) affecting glucocorticoid sensitivity. Testicular function was determined by semen analysis and reproductive hormone profiling in 893 men from the general population. The NR3C1 SNP BclI was associated with semen quality in an over-dominant manner with heterozygotes having better semen parameters compared to both homozygote constellations, and with sperm motility showing the strongest association. This association was supported by a higher inhibin B and inhibin B/FSH ratio, as well as a lower FSH in BclI heterozygotes. The SNPs 9β and Tth111I were not associated with semen parameters. Although the clinical impact of the findings is limited, the results substantiate a suggested link between stress and testicular function. Hence this investigation should be regarded as a discovery study generating hypotheses for future studies.

Abstract MIP-063: DEFINING NOVEL PARACRINE FUNCTIONS FOR INHIBIN IN OVARIAN CANCER

Abstract BACKGROUND AND SIGNIFICANCE: Inhibins are members of the TGF-β superfamily loss of which in mice results in gonadal tumorigenesis. In humans, Inhibin is elevated in patients across several ovarian cancer subtypes including GCT's, mucinous, clear cell, to lesser extents in high grade serous and also in the stroma of Brenner tumors as reported by several others. Other cancers with elevated Inhibin include prostate and common cancers associated with ascites accumulation such as colon, gastric, and pancreatic. The Type III TGF-β receptor/ Betaglycan is the only high affinity receptor molecule that has been shown to directly bind Inhibin, that does not induce signaling, but is frequently lost in ovarian cancer as reported previously. The overall goal of our studies supported in part by the Rivkin Center for Ovarian Cancer were to 1) define the possible functional consequences of elevated Inhibin in cancers in the absence of Betaglycan, 2) determine whether elevated Inhibin may act as a tumor-promoter via a novel complement of receptors in the absence of Betaglycan and 3) to evaluate the impact of blocking inhibin using a neutralizing antibody on ovarian cancer growth and metastasis. RESULTS: We find that Inhibin (alpha subunit, INHA) is largely expressed by multiple ovarian cancer epithelial cells with Inhibin A significantly elevated in the ascites of ovarian cancer patients. Reducing autocrine production of Inhibin by silencing expression of the alpha subunit in epithelial cells has only modest effects on invitro cancer cell growth, migration and invasion either in the presence or absence of Betaglycan. However, most strikingly, we find that conditioned media from ovarian cancer cells with high Inhibin levels rapidly induce SMAD1/5 activation in a paracrine manner on endothelial cells. We find that both recombinant InhibinA and paracrine Inhibin are activators of endothelial cell signaling and angiogenesis both in -in vitro endothelial differentiation assays and in vivo in mice. Mechanistically, Inhibin utilizes an alternate endothelial receptor complement system, components of which are elevated in the ascites of ovarian cancer patients. Antibodies to both the receptors recognizing Inhibin and Inhibin itself suppress Inhibin induced endothelial cell differentiation and angiogenesis. Additionally, Inhibin is a more robust mediator of angiogenesis as compared to TGF-β or Activin and can synergize with VEGF to stimulate endothelial cell differentiation and angiogenesis. IMPLICATIONS: We have discovered a new mechanism and function for Inhibin that may be relevant for ovarian cancer subtypes and pathologies that present elevated Inhibin. While current anti-angiogenic therapies targeting VEGF show promise for the treatment of advanced ovarian cancers, significant side effects and toxicities exist. Our findings on the paracrine role of Inhibin that is normally at extremely low levels in postmenopausal women suggest that consideration of anti- Inhibin antibodies in conjunction with anti- VEGF therapies may hold promise in the future. These findings will be presented and discussed. Citation Format: Priyanka Singh, Laura Jenkins, Kathleen O'Connell, YingMiao Liu, Andy Nixon, and Mythreye Karthikeyan. DEFINING NOVEL PARACRINE FUNCTIONS FOR INHIBIN IN OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-063.

Serum Inhibin A and Inhibin B Levels in Epithelial Ovarian Cancer Patients

The aimof our study was to examine serum inhibin A and inhibin B concentrations in ovarian cancer patients in relation to clinicopathological features and 5-year survival.Material and MethodsWe enrolled 90 epithelial ovarian cancer patients in our study, aged 45–81 years, who underwent optimal cytoreductive surgery. In all patients, serum inhibin A and inhibin B concentrations were measured using a two-step sandwich type enzyme immunoassay before surgery.ResultsIn the group of patients with ovarian cancer median serum concentration of inhibin A was 3.87 pg/mL (0.96–10.09) and inhibin B was 13.9 pg/mL (5.1–45.0). Median concentrations of inhibin A and B in relation to FIGO stage and histological subtype did not differ significantly. Inhibin A levels were significantly higher in patients with lower grading (G1 and G2) in comparison to those with higher grade G3 (p = 0.001). There were no differences in inhibin B concentrations in relation to grading. The Kaplan-Meier analyses demonstrated no differences in survival rate in relation to inhibin A levels, while there was a stepwise impairment of 5-years survival with increased inhibin B level. In the group of patients with inhibin B levels higher than 20 pg/ml the survival rate was lower (p = 0,00625, log-rank test).Conclusion1. Higher inhibin A serum levels were found in patients with highly differentiated ovarian carcinoma compared to the group of patients with a poorly differentiated cancer, which may confirm the influence of inhibin A on cell proliferation processes. 2. A significant importance of inhibin B was demonstrated in the prediction of death within less than a five year period. The probability of survival in patients featuring high inhibin B levels was lower with statistical significance. This may indicate the need for further studies on how to block the inhibin B activation pathway in the ovarian carcinoma therapy.

Gonadectomy-related adrenocortical tumors in ferrets demonstrate increased expression of androgen and estrogen synthesizing enzymes together with high inhibin expression

The 2 objectives of this study were to (1) measure by quantitative polymerase chain reaction the expression of genes involved in steroid and inhibin synthesis in adrenocortical tumors of gonadectomized ferrets and (2) localize by immunohistochemistry several proteins that are key to adrenal steroidogenesis. Relative to the control adrenals, expression of the messenger RNAs encoding StAR (steroidogenic acute regulatory protein; P = 0.039), CYP11A (P = 0.019), CYP21 (P = 0.01), and 3β-HSD (P = 0.004), all involved in the synthesis of mineralocorticoids and glucocorticoids, were decreased in the adrenocortical tumors. In contrast, expression of cytochrome B5 (CytB5; P = 0.0001) and aromatase (P = 0.003), involved in androgen and estrogen synthesis, and both inhibin α-subunit (P = 0.002) and βB-subunit (P = 0.001) were upregulated. In tumors, immunostaining of CYP21 was low, whereas staining of Cyp17 and CytB5, necessary for androgen synthesis, was present. It is concluded that ferret adrenocortical tumors express genes for androgen production. In addition, the expression of aromatase and inhibin suggests an even more gonadal differentiation, which is reminiscent to the fact that both gonads and adrenals are derived from a common urogenital primordial cell.

Peripubertal changes in circulating antimüllerian hormone levels in girls

ObjectiveTo identify correlates and longitudinal changes in circulating antimüllerian hormone (AMH) levels as a marker of ovarian primordial follicle recruitment in normal peripubertal girls.DesignObservational study using mixed longitudinal and cross-sectional analyses.SettingNot applicable.Patient(s)Unselected girls assessed at ages 7–11 years.Intervention(s)None.Main Outcome Measure(s)AMH, inhibin B, and FSH levels were analyzed in blood samples collected at ages 7, 9, and 11 years for longitudinal analyses and at age 8 years for cross-sectional analyses.Result(s)In the cross-sectional analysis, AMH levels at age 8 years were lower in pubertal girls (median 25.0 pmol/L, interquartile range [IQR] 16.0–33.9; n = 39) than in prepubertal girls (33.5 pmol/L, IQR 22.3–49.1; n = 342). In prepubertal girls, higher AMH levels were associated with higher inhibin B levels, lower FSH levels, and larger body mass index at age 8 years and subsequently with later age at menarche. AMH levels were unrelated to birth weight or birth length. In the longitudinal analysis, AMH levels increased between ages 7 (median 27.0 pmol/L, IQR 19.2–34) and 9 years (32.0 pmol/L, IQR 26.5–42.7), then declined between 9 and 11 years (26.5 pmol/L, IQR 19–42.25) with high intraindividual correlation in AMH levels between ages 7 and 9 years and 7 and 11 years.Conclusion(s)Measurement of circulating AMH and inhibin B levels suggests that the rate of ovarian primordial follicle recruitment increases in the prepubertal years then declines again following the onset of puberty as follicular activity pattern changes.

Elevated serum progesterone at end of stimulation with recombinant FSH, but not with highly purified menotropin, is associated with poor outcome in GnRH antagonist cycles

To investigate the impact on treatment outcome of elevated progesterone at end of stimulation in a GnRH antagonist cycle. Retrospective investigation of an RCT. Data from 749 patients undergoing COS in a GnRH antagonist cycle with highly purified menotropin (HP-hMG, MENOPUR, Ferring Pharmaceuticals) or rFSH (FOLLISTIM, Merck) using 150 IU for the first five days and adjusted individually thereafter [MEGASET; ClinicalTrials.gov NCT00884221]. Blood was drawn on stimulation day 1, day 6 and at end of stimulation, and analysed centrally. Ongoing pregnancy rate (OPR) (10-11 weeks after single blastocyst transfer) and clinical profiles were compared according to serum progesterone at end of stimulation using 4 nmol/L as cut-off. Progesterone > 4 nmol/L at end of stimulation was similarly frequent with HP-hMG (16%) and rFSH (14%). The OPR in the progesterone > 4 nmol/L and ≤ 4 nmol/L groups was 16% and 29% for rFSH (P<0.05) and 29% and 30% for HP-hMG, respectively. For patients with transfer, the OPR was 21% and 33% with rFSH, and 35% and 35% with HP-hMG, respectively. In both treatment groups, patients with progesterone > 4 nmol/L at end of stimulation had significantly (P<0.001) higher progesterone and testosterone on day 1, higher progesterone and LH on day 6, and higher estradiol, progesterone, estradiol/progesterone ratio, testosterone and SHBG at the end of stimulation as well as more oocytes retrieved. Those in the rFSH group also had significantly (P<0.001) lower FSH on day 1, higher inhibin B on day 6 and higher FSH on day 6 and at end of stimulation. There were no major differences in endometrial profile or blastocyst quality. Elevated progesterone at the end of stimulation in a GnRH antagonist cycle is associated with follicular steroidogenesis and higher ovarian response irrespective of type of gonadotropin used, but only with a significantly lower ongoing pregnancy rate when stimulated with rFSH and not with HP-hMG.

Identification by array-Comparative Genomic Hybridization (array-CGH) of a large deletion of luteinizing hormone receptor gene combined with a missense mutation in a patient diagnosed with a 46,XY disorder of sex development and application to prenatal diagnosis

This paper reports the case of an infant presenting with sexual ambiguity at birth. The child presented with labia majora synechia, thready genital tubercle and perineal hypospadias. The karyotype was 46,XY. Low testosterone levels with no response to hCG administration, associated with high LH level for her age, high FSH level, high inhibin B levels and normal AMH indicated a lack of LH receptivity and prompted us to screen the LHCGR gene for mutations. A previously described missense mutation (p.Cys131Arg) was identified at homozygous state in the propositus and at heterozygous state in the mother. This variation, however, was not found in the father. Our attention was drawn by the presence of several single nucleotide polymorphisms (SNPs), identified at homozygous state without any paternal contribution from exon 1 to exon 10 of LHCGR, suggesting a paternal deletion. Array DNA analysis was performed revealing a large deletion extending from 61,493 to 135,344 bp and including the LHCGR gene. Adequate genetic counselling was provided. This paper describes the first application of prenatal diagnosis in LHCGR deficiency for 46,XY disorders of sex development with the subsequent delivery of a normal baby.

Influence of Preterm Birth and Birth Size on Gonadal Function in Young Men

Preterm birth has been associated with reduced reproduction rates and being born small for gestational age (SGA) with reduced gonadal function. We hypothesized that alterations concerning gonadal function in young men are not due to preterm birth or being born SGA, but are due to other (environmental) factors. In 207 young men of the PROGRAM/PREMS cohort study, aged 18-24 yr, the influence of preterm birth, birth length, and birth weight on serum levels of anti-Mullerian hormone, inhibin B, testosterone, SHBG, non-SHBG-bound testosterone, LH, and FSH was analyzed with multiple regression modeling. In addition, markers of male gonadal function were analyzed in four subgroups: men born SGA with either short stature or catch-up growth, or men born appropriate for gestational age with idiopathic short stature or with normal stature (control). Preterm birth and SGA did not affect gonadal function. After adjustment for age, birth size, adult height, fat mass, and socioeconomic status (SES), preterm birth even showed a positive relation with inhibin B. Higher SES was associated with higher inhibin B levels. Higher fat mass was associated with decreased testosterone and SHBG levels and maternal smoking with increased LH and non-SHBG-bound testosterone levels. After adjustment for confounders, there were no significant differences in gonadal function between the subgroups. Preterm birth and SGA did not affect gonadal function in young men. Factors that affected gonadal function were: lower SES, a higher fat mass, and maternal smoking during pregnancy.

Subfertility Caused by Altered Follicular Development and Oocyte Growth in Female Mice Lacking PKBalpha/Akt11

Mammalian females are endowed with a finite number of primordial follicles at birth. Immediately following formation of the primordial follicle pool, cohorts of follicles are either culled from the ovary or are recruited to grow until the primordial follicle population is depleted. The majority of ovarian follicles, including the oocytes, undergo atresia through apoptotic cell death. As PKBalpha/Akt1 is known to regulate apoptosis, we asked whether Akt1 functioned in the regulation of folliculogenesis in the ovary. Akt1−/− females display reduced fertility and abnormal estrous cyclicity. At Postnatal Day (PND) 25, Akt1−/− ovaries possessed a reduced number of growing antral follicles, significantly larger primary and secondary oocytes, and an increase in the number of degenerate oocytes. By PND90, there was a significant decrease in the number of primordial follicles in Akt1−/− ovaries relative to Akt1+/+. In vivo granulosa cell proliferation was reduced, as were expression levels of Kitl and Bcl2l1, two factors associated with granulosa cell proliferation/survival. No compensation was observed by Akt2 or Akt3 at the mRNA/protein level. Significantly higher serum LH and trends for lower FSH and higher inhibin A and lower inhibin B relative to Akt1+/+ females were observed in Akt1−/− females. Exposure to exogenous gonadotropins resulted in an increase in the number of secondary follicles in Akt1−/− ovaries, but few mature follicles. Collectively, our results suggest that PKBalpha/Akt1 plays an instrumental role in the regulation of the growth and maturation of the ovary, and that the loss of PKBalpha/Akt1 results in premature ovarian failure.

Secondary amenorrhoea with high inhibin B level caused by parasitic ovarian leiomyoma

Secondary amenorrhoea with high inhibin B level caused by parasitic ovarian leiomyoma

Maternal smoking in pregnancy and reproductive hormones in adult sons

Smoking during pregnancy has been reported to alter levels of reproductive hormones in adult sons. From a Danish pregnancy cohort established in 1984-1987, 347 out of 5109 sons were selected according to their exposure to tobacco smoke in foetal life. From February 2005 to January 2006, a blood sample from each young man (18-21 years) was collected and analysed for reproductive hormones. There were no apparent trends of increasing or decreasing hormonal levels with increased exposure to maternal tobacco smoking during pregnancy. Only the free testosterone/free estradiol ratios increased with increased maternal smoking during pregnancy (p for trend = 0.05). No trends for increasing odds ratios for high follicle-stimulating hormone (> or =25 percentile) or low inhibin B (< or =25 percentile) in relation to maternal smoking were observed. We found no major indication of long-term effects of pre-natal exposure to tobacco smoke on the levels of reproductive hormones later in life, but the data may suggest a shift in the hypothalamo-pituitary-gonadal axis towards higher androgenicity. This result was, however, of only borderline significance and could be because of chance.

High Serum Inhibin Concentration Discriminates Autoimmune Oophoritis from Other Forms of Primary Ovarian Insufficiency

High Serum Inhibin Concentration Discriminates Autoimmune Oophoritis from Other Forms of Primary Ovarian Insufficiency

Very High Inhibin A Concentration Attributed to Heterophilic Antibody Interference

Maternal serum screening for Down syndrome is commonly performed in the 2nd trimester using α fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A. Concentrations of each marker are combined with maternal age to calculate a patient-specific risk of fetal Down syndrome. In cases of Down syndrome, inhibin A concentration is, on average, approximately twice as high as in unaffected singleton pregnancies (1). Second trimester maternal serum inhibin A is also increased in twin pregnancies [1.99 multiples of the median (MoM) (1)] and in Turner syndrome with hydrops (3.91 MoM; (2)). Markedly increased inhibin A has been observed in pregnancies with complete hydatidiform mole [4–7 MoM; (3)]. Increased inhibin A may also be seen in nonpregnant women with ovarian cancer (4). We describe a woman having 2nd trimester serum inhibin …

In this edition

In this edition