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Biomedical subjects

N Groome

Publications and source records attributed to N Groome.

At least 19 recordsLinked to original sources
PubMed2002

Inhibins/activins as diagnostic markers for ovarian cancer.

It is widely recognised that the early detection and subsequent assessment of recurrence of ovarian cancers are key steps for successful treatment. Available serum markers (e.g. CA125) are sensitive for some epithelial carcinomas (e.g. serous, endometrioid, clear cell), however, these markers are less sensitive for granulosa cell tumours and mucinous carcinomas. Serum inhibin is an ovarian product which decreases to non detectable levels after menopause, however, certain ovarian cancers (mucinous carcinomas and sex cord stromal tumours such as granulosa cell tumours) continue to produce inhibin which provides a basis for a serum diagnostic test. Studies from this and other laboratories have investigated the suitability of inhibin as a diagnostic marker by identifying which inhibin (inhibin A (alphabetaA), inhibin B (alphabetaB), free alpha subunit) or activin (betaAbetaA) form is associated with these cancers. Available data show that inhibin assays which detect all inhibin forms, i.e. assays which detect the alpha subunit both as the free form and as an alphabeta subunit dimer provide the highest sensitivity/specificity characteristics as an ovarian cancer diagnostic test. This review will discuss the data supporting these observations and show recent studies in which a new alpha subunit monoclonal antibody-based ELISA is used as a potential diagnostic test. Furthermore, based on the high sensitivity/specificity characteristics of the respective assays for the various types of ovarian cancer, the combination of the inhibin assay with CA125 detects the majority of all ovarian cancers.

Activins↗
PubMed2002

Serum inhibins, estradiol, progesterone and FSH in surgical menopause: a demonstration of ovarian pituitary feedback loop in women.

BACKGROUND: The objective of this study was to confirm the source and study the acute changes and relationship between inhibins and FSH at surgical menopause. METHODS: Regularly cycling women (42-47 years; n = 10) undergoing bilateral oophorectomy for non-ovarian pathology were recruited for this study. One blood sample was taken before surgery and after removal of the ovaries, samples were taken every 15 min up to 1 h, hourly up to 6 h, after 12 h and daily during the hospital admission (3 days). RESULTS: There were five women in the follicular phase and five women in the luteal phase of the cycle. For women in both phases, levels of inhibin A, inhibin B, estradiol (E(2)) and progesterone decreased after the removal of the ovaries. Serum FSH levels started to rise after 12 h in both follicular and luteal phase women after the surgical menopause. Correlation analysis showed that inhibin A and E(2) were significantly negatively correlated in both phases with FSH concentration. Inhibin B had a negative correlation in the follicular phase and progesterone had a negative correlation in the luteal phase. CONCLUSIONS: This study showed that ovarian inhibin A and B were cleared from the circulation within 12 h of oophorectomy, whereas E(2) and progesterone remain in the circulation for longer. Negative correlation between FSH, inhibin A and inhibin B suggests that inhibins may contribute to the observed early rise in FSH after the surgical menopause.

Adult↗
PubMed2002

Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages.

BACKGROUND: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss. METHODS: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone. RESULTS: Serum inhibin A, hCG, estradiol and progesterone levels were significantly ( approximately 2-3 fold) decreased in sporadic miscarriages compared with controls. In the recurrent miscarriage group, time dependent changes in plasma inhibin A and hCG levels were significantly (P < 0.05) altered in the group that had a subsequent miscarriage compared with those who had a live birth. At 6-7 weeks gestation, plasma inhibin A ( approximately 4 fold, P < 0.01), hCG ( approximately 4 fold, P < 0.01) and estradiol ( approximately 2 fold, P < 0.001) levels were significantly lower in women who went on to have another miscarriage than those with a live birth. Inhibin B levels were near the detection limit of the assay. CONCLUSIONS: Our findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage. There is a high degree of association between levels of inhibin A and hCG in cases of miscarriage, indicating that these two proteins could be used in combination to predict future pregnancy outcome.

Abortion, Habitual↗
PubMed2002

Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome.

BACKGROUND: Day 5 serum inhibin B during IVF treatment has been investigated as a predictor of outcome. METHODS: A total of 54 women (< or = 39 years, normal menses and endocrine profiles) were treated with urinary gonadotrophins or recombinant FSH following pituitary down-regulation. Serum day 3 FSH in a preceding cycle was <8.5 IU/l. Plasma inhibin B, inhibin A and estradiol were determined after 4 days of gonadotrophin administration (day 5). RESULTS: Day 5 inhibin B was the most highly correlated with the number of mature follicles (>14 mm), oocytes retrieved and fertilized. Receiver operating characteristic analysis gave high accuracy for day 5 inhibin B in predicting ovarian response and indicated that a threshold of 400 pg/ml may be helpful in the decision as to whether to continue treatment. Women with <400 pg/ml (n = 16) had lower numbers of follicles, mature follicles, oocytes retrieved, fertilized and cleaved compared with those >400 pg/ml (n = 36) and this threshold gave a positive likelihood ratio of 30, 92.9% sensitivity, 95.0% specificity and 86.7% positive predictive value to detect poor ovarian response. Day 5 inhibin B was the best predictor of pregnancy (no live births and four cycles cancelled, low inhibin group; nine live births and no cancelled cycles, high inhibin group). CONCLUSIONS: Normogonadotrophic, normogonadal women with day 5 inhibin B <400 pg/ml in down-regulated cycles have a poor response to ovarian stimulation and are less likely to conceive compared with women with higher day 5 inhibin B.

Adult↗
PubMed2002

Characterization of inhibin forms and their measurement by an inhibin alpha-subunit ELISA in serum from postmenopausal women with ovarian cancer.

The aim of this study was to characterize the molecular wt forms of inhibins A and B and its free alpha-subunit present in serum from women with ovarian cancer as a basis for developing improved monoclonal antibody-based inhibin assays for monitoring ovarian cancer. Three new inhibin alpha-subunit (alphaC) ELISAs were developed using monoclonal antibodies directed to three nonoverlapping peptide regions of the alphaC region of the inhibin alpha-subunit. To characterize serum inhibin molecular wt forms present in women with ovarian cancer, existing inhibin immunoassays (inhibin A, inhibin B, and pro-alphaC) and the new alphaC ELISAs were applied to sera from women with granulosa cell tumors and mucinous carcinomas previously fractionated using a combined immunoaffinity chromatography, preparative SDS-PAGE, and electroelution procedure. The distribution and molecular size of dimeric inhibins and alpha-subunit detected were consistent with known mol wt forms of inhibins A and B and inhibin alpha-subunit and their precursor forms present in serum and follicular fluid from healthy women. The alphaC ELISAs recognized all known forms of inhibin and the free inhibin alpha-subunit, although differences between alphaC ELISAs were observed in their ability to detect high mol wt forms. To assess which of the alphaC ELISAs was preferred in application to ovarian cancer, the alphaC ELISAs were applied to serum from a range of normal postmenopausal women (n = 61) and postmenopausal women (n = 152) with ovarian (serous, mucinous, endometrioid, clear cell carcinomas, and granulosa cell tumors) and nonovarian (breast and colon) cancers. Despite differences in their ability to detect high mol wt forms of inhibin, the alphaC ELISAs showed similar sensitivity (i.e. proportion of cancer patients correctly detected) and specificity (proportion of controls correctly detected) indexes in the detection of mucinous carcinomas (84% and 95%) and granulosa cell tumors (100% and 95%) compared with earlier inhibin RIA or polyclonal antibody-based immunofluorometric assays. A combination of the alphaC ELISAs with the CA125 assay, an ovarian tumor marker that has a high sensitivity and specificity for other ovarian cancers (serous, clear cell, and endometrioid), resulted in an increase in sensitivity/specificity indexes (95% and 95%) for the all ovarian cancer group. These new monoclonal antibody-based inhibin alphaC ELISAs now provide practical and sensitive assays suitable for evaluation as diagnostic tests for monitoring ovarian cancers.

Adenocarcinoma, Mucinous↗
PubMed2002

Expression and dimerization of the rat activin subunits betaC and betaE: evidence for the ormation of novel activin dimers.

Activins are cytokines of the transforming growth factor beta family, which plays a central role in the determination of cell fate and the regulation of tissue balance. Family members are composed of two subunits and this dimerization is critical for liganding their cognate receptors and execution of proper functions. In the current study we focused on the localization of activin betaA, betaB, betaC and betaE subunits in the adult rat and analyzed the composition of putative activin beta dimers. By dissecting tissue distribution of various activins, we found that the liver, in particular the hepatocytes, is the major source for activin betaC and betaE transcripts, since other tissues almost failed to express these isoforms. In sharp contrast, the emergence of activin betaA and betaB appeared ubiquitous. Using a highly selective proteome approach, we were able to identify homo- as well as heterodimers of individual activin subunits, indicating a high redundancy of ligand composition. Certainly, this broad potential to homo- and heterodimerize has to be considered in future studies on activin function.

Activins↗
PubMed2001

Development of an inhibin alpha subunit ELISA with broad specificity.

Inhibin immunoassays with a sufficiently broad specificity to detect all alpha subunit-containing forms are of value in detecting and monitoring various ovarian cancers. Assays to date with this specificity are not readily amenable to wide diagnostic application. The objective of this study was to develop a sensitive two-site ELISA using alpha subunit-directed monoclonal antibodies (Mabs) able to detect all forms of inhibin to replace a previously described alpha subunit-directed immunofluorometric assay (IFMA). In this study, the major inhibin epitopes in the two polyclonal antisera used in the alphaC IFMA were initially identified and Mabs were raised to these regions. These Mabs in conjunction with the inhibin alpha subunit R1 Mab (Groome) were used to develop alpha subunit ELISAs with high sensitivity. Application of these assays to human serum and human follicular fluid following fractionation by an immunoaffinity/preparative PAGE/electroelution procedure which separated inhibins according to their molecular weights, indicated that the specificity of the various ELISAs differed between Mab combinations with preferences noted for either the alpha subunit or dimeric forms. A combination of Mabs in an ELISA was identified which provided data which matched that obtained with the alphaC IFMA and which may be useful as a replacement inhibin assay in clinical studies.

Animals↗
PubMed2001

The effect of gonadotrophins with differing LH/FSH ratios on the secretion of the various species of inhibin in women receiving IVF.

We have measured secretory patterns of inhibin A, B, total alpha inhibin, pro-alphaC inhibin and oestradiol in women following pituitary suppression who were randomised into two groups to receive either urinary gonadotrophin (25:75 IU/ampoule of luteinizing hormone (LH) and follicle stimulating hormone (FSH; Normegon; n = 11) or recombinant (r)FSH (75 IU/ampoule of FSH alone, n = 16). The women were of similar age (approximately 33 years) and length of infertility (approximately 4 years) and had a normal endocrine evaluation. Plasma FSH, LH, oestradiol, inhibin A, B, pro-alphaC and total alpha inhibin were measured by immunoassay prior to and following gonadotrophin stimulation. Immunoactive FSH, LH and oestradiol blood concentrations following pituitary down regulation were similar in the two groups being <2.0, <3.6 IU/l and <82 pmol/l respectively. The units of FSH given (2230 versus 2764 IU; Normegon versus rFSH), duration of treatment (9.1 versus 9.4 days) and number of follicles of > or =14mm on the day of human chorionic gonadotrophin (HCG) administration (17 versus 14) were also similar. Inhibin A or B concentrations rose similarly during Normegon or rFSH administration, peaking at days 9-11. Total alpha and pro-alphaC inhibin concentrations were lower (P < 0.05) in the rFSH group during days 10 and 11 of treatment being 18.9 +/- 15.9 ng/ml (Normegon) and 4.6 +/- 2.8 ng/ml (rFSH) for total alpha inhibin and 8.5 +/- 6.8 ng/ml (Normegon) and 2.8 +/- 1.6 ng/ml (rFSH) for pro-alphaC inhibin on day 10. Overall, higher total alpha inhibin concentrations were associated with more mature follicles and oocytes, greater fertilization rates and better quality embryos. We conclude that inhibin A and B secretion was similar in both groups and is primarily controlled by FSH, whereas total alpha inhibin and pro-alphaC increased preferentially in the Normegon group over the rFSH group, indicating that they are, in part, stimulated by LH.

Adult↗
PubMed2001

Changes in molecular weight forms of inhibin A and pro-alpha C in maternal serum during human pregnancy.

Maternal serum pools obtained from healthy women throughout normal pregnancy were fractionated by a combined immunoaffinity chromatography, preparative PAGE, and electroelution procedure. Inhibin A and the pro-alpha C region of the inhibin alpha-subunit were determined in the eluted fractions by specific ELISAs, and the profiles of immunoactivity characterized in terms of molecular weight and percent recovery. The molecular weight patterns of inhibin A and pro-alpha C in serum during early pregnancy (<19 wk gestation) showed peaks between 25-40K and approximately 60K, consistent with the presence of known mature and larger precursor inhibin forms. However, during late pregnancy (>19 wk gestation), an increase in the proportion of smaller molecular weight forms (from 2% to approximately 25%) of inhibin A and pro-alpha C of unknown structure were observed in the less than 30K and less than 25K regions, respectively. To assess whether this change in molecular weight distribution in late pregnancy was related to the method of serum collection, serum and plasma from women during early and late pregnancy were collected and snap-frozen. Three pools [one from early pregnancy (12-15 wk), two from late pregnancy (28-39 wk)] of serum and plasma were then fractionated as described above. No differences in molecular weight patterns of inhibin A and pro-alpha C were observed between serum and plasma pools obtained in early pregnancy. However, in late pregnancy there was a reduction in the proportion of low molecular weight forms between serum (25% inhibin A, 35% pro-alpha C) and plasma (12% and 17%, respectively), but not to the low levels seen in early pregnancy. Incubation of iodinated 30K human inhibin A with serum or plasma obtained from early or late pregnancy showed no evidence of cleavage, suggesting that 30K inhibin A is not the cleavage precursor. It is speculated that the formation of small molecular weight forms of both inhibin A and pro-alpha C is attributed to proteolytic changes, in part induced in the circulation during late gestation and in part by the placenta before secretion. It is concluded that inhibin A and pro-alpha C are processed in late pregnancy by more than one mechanism to form low molecular weight circulating forms of unknown structure.

Chemical Fractionation↗
PubMed2001

Serum activin A and follistatin in disorders of spermatogenesis in men.

OBJECTIVE: Inhibin, activin and follistatin are glycoprotein hormones produced by the gonads. Recent studies have shown that inhibin B is the predominant form of inhibin in the circulation in men. The objective of this study was to investigate circulating levels of activin A and follistatin in disorders of spermatogenesis in men and their relationship with FSH and inhibin B. DESIGN AND METHOD: Serum from five different groups of men was prospectively collected and stored at -20 degrees C. The groups were men with: (i) proven fertility (controls) (n=20), (ii) primary testicular failure (n=15), (iii) obstructive azoospermia (n=10), (iv) oligospermia (n=10) and (v) miscellaneous sperm dysfunction (n=40). WHO criteria (1992) were used for semen characterisation. Serum concentrations of 'total' activin A, follistatin, FSH and inhibin B were measured using specific two-site enzyme immunoassays. RESULTS: Activin A levels were significantly lower than in the controls in the obstructive azoospermia group and higher in the miscellaneous sperm dysfunction group. Serum follistatin levels did not significantly vary in any group compared with the controls. Circulating levels of FSH were higher than in the controls in the primary testicular failure and obstructive azoospermic group. Levels of inhibin B were lower than in the controls in all disorders of spermatogenesis studied. CONCLUSION: This study demonstrates that activin A and follistatin are in the circulation in males and activin A levels are significantly lower in obstructive azoospermia and higher in miscellaneous sperm dysfunction than in controls. The mechanism involved in altering the levels of activin A in these conditions is not clear. However, high follistatin:activin A molar ratios (>2.5) in all groups suggests that all activin A in the circulation is bound to follistatin in males.

Activins↗
PubMed2000

Temporal analysis of growth factor mRNA expression in myelinating rat brain aggregate cultures: increments in CNTF, FGF-2, IGF-I, and PDGF-AA mRNA are induced by antibody-mediated demyelination.

Myelinogenesis in rat brain aggregate cultures is associated with a pattern of growth factor mRNA expression comparable to that of the developing brain. The rate of increase in platelet-derived growth factor-AA (PDGF-AA) expression was greatest just before the detection of myelin basic protein (MBP) mRNA in the cultures and remained high thereafter, consistent with in vivo observations. Levels of fibroblast growth factor-2 (FGF-2) and of ciliary neurotrophic factor (CNTF) mRNA increased continuously over the period of MBP accumulation. High rates of transforming growth factor beta1 (TGF-beta1), insulin-like growth factor-I (IGF-I), and neurotrophin-3 (NT-3) expression at early time points during the culture gradually decreased over time, indicative of a key regulatory role during oligodendrocyte development. The addition of demyelinative anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody resulted in a significant increase in MBP peptide fragments with a C-terminus at phenylalanine 89 indicating proteolytic breakdown of MBP after myelin phagocytosis. Immediately after antibody treatment the expression of CNTF mRNA was significantly increased, compared with controls, while that of FGF-2 and IGF-I, and of PDGF-AA peaked during the early and later stages of recovery respectively. Thus, specific growth factors combine to regulate myelination and remyelination in the aggregates; these data have implications for demyelinating disease in which protective growth factor secretion may be central to regeneration.

Animals↗
PubMed2000

Inhibins A and B are regulated differentially in the early post-partum period.

BACKGROUND: The early postpartum period is characterized endocrinologically by a rapid fall in the levels of oestradiol (E2) and immunoreactive inhibin, and a delayed rise in serum follicle stimulating hormone (FSH). No description is currently available of changes in serum inhibins A and B. OBJECTIVES: The present study aimed to examine the levels of inhibin A and B during the early weeks of postpartum lactational amenorrhoea, to determine whether there was evidence for differential regulation of the two hormones at a time when no dominant follicle was developing in the ovary. SUBJECTS AND METHODS: Serum samples were available from 12 subjects aged 29-38 in whom postpartum levels of FSH, immunoreactive inhibin, E2 and prolactin had been examined previously. Samples for hormone assays had been obtained prior to delivery, daily for the 3-5 days postpartum, and weekly thereafter. Inhibins A and B were measured by specific ELISA assays, and results were calculated as 10 day averages for samples obtained on days 1-10, 11-20, 21-30, etc. postpartum. Normal hormone concentrations for reference were obtained from volunteers, also aged 29-38, sampled on days 3-5 of a normal menstrual cycle. RESULTS: Inhibin A in the predelivery sample ranged from 62 to 1243 ng/l, geometric mean 592. Concentrations fell rapidly postpartum and reached a nadir in the low follicular phase range between days 5 and 37 postdelivery, mean 13.6 days. The concentrations of both inhibin B and FSH rose 14-27 days postpartum from their initially low postdelivery levels, to reach the normal follicular phase range. These increases in concentration were significantly correlated in all individual subjects. CONCLUSIONS: The secretion of inhibin A and B is regulated differentially during the early stages of lactational amenorrhoea, just as it is in the late luteal phase of the normal menstrual cycle. Whilst inhibin A falls postpartum, reflecting cessation of placental function, and remains low until ovulatory cycles are resumed, FSH and inhibin B rise after a delay of two weeks or more. It is postulated that the rise of inhibin B is the result of secretion from a cohort of small follicles stimulated by rising FSH levels.

Adult↗
PubMed2000

Serum inhibin A and activin A are elevated prior to the onset of pre-eclampsia.

Serum inhibin A and activin A concentrations increase in pre-eclampsia. We investigated the time courses of the changes in relation to the onset of the maternal syndrome and if their measurement could be useful for clinical prediction particularly in relation to early onset disease, the most severe of the clinical presentations. Serial samples were taken from 1496 healthy nulliparae. Changes in activin A and inhibin A were analysed in women with: early onset pre-eclampsia (n = 11), pre-eclampsia delivering at 34-36 weeks (n = 14), term pre-eclampsia (n = 25) and gestational hypertension (n = 25); and in a subset with uncomplicated pregnancies (n = 25). Serum inhibin A and activin A were increased in all groups prior to pre-eclampsia, before 20 weeks in those with early onset pre-eclampsia. Screening efficacy was determined at 15-19 and 21-25 weeks in all women who developed pre-eclampsia (n = 70) and randomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for early onset pre-eclampsia: 67 and 44% at 15-19 weeks and 89 and 89% at 21-25 weeks for inhibin A and activin A respectively. Hence, serum inhibin A and activin A concentrations increase before the onset of pre-eclampsia at gestational ages that depend on when pre-eclampsia develops. On their own such measures are unlikely to prove efficient for screening.

Activins↗
PubMed2000

Relationship between serum inhibin A and B and ovarian follicle development after a daily fixed dose administration of recombinant follicle-stimulating hormone.

The aim of this study was to investigate the relationship of serum inhibin A and inhibin B to ovarian follicular development in women undergoing pituitary down-regulation and ovarian stimulation with a fixed daily dose of recombinant human FSH in an in vitro fertilization program. Thirty-eight patients were treated randomly with either 100 or 200 IU/day recombinant human FSH (Puregon) for a period of 9-14 days. Serum FSH, inhibin A, inhibin B, 17beta-estradiol, and follicular size and number were determined before FSH treatment and every second day from days 4-6 throughout FSH treatment. Serum FSH increased in a dose-related manner to reach a maximum by days 4-6 and remained unchanged over the duration of treatment. Serum inhibin A and 17beta-estradiol also increased with increasing FSH dose and continued to rise throughout the FSH treatment period. By contrast, serum inhibin B was increased by days 4-6 at both doses of FSH to reach a maximum by days 7-8, remaining unchanged thereafter. Serum inhibin B and, to a lesser extent, inhibin A correlated significantly with the number of oocytes retrieved even when assessed early (days 4-6) in the treatment period (inhibin B vs. number of oocytes: r = 0.89; P < 0.001; inhibin A vs. number of oocytes: r = 0.61; P < 0.05). Serum inhibin A, inhibin B, and 17beta-estradiol were weakly correlated with the number of follicles less than 11 mm when assessed on a daily basis; stronger correlations were observed with the greater than 11-mm follicles during the late stages of treatment. It is concluded that serum inhibin B levels determined during the early stages (e.g. days 4-6) of fixed dose FSH treatment provide an early indicator of the number of recruited follicles that are destined to form mature oocytes. In this context, serum inhibin B may be of predictive value in monitoring ovarian hyperstimulation treatment for in vitro fertilization.

Adult↗
PubMed2000

Early follicular phase serum FSH as a function of age: the roles of inhibin B, inhibin A and estradiol.

OBJECTIVE: Reproductive aging in regularly cycling normal women is characterized by a gradual decline in ovarian follicle number and a progressive increase in serum follicle stimulating hormone (FSH), particularly over the age of 40 years. The lack of any consistent decrease in circulating estradiol and progesterone has led to the hypothesis that the FSH increase results from decreasing ovarian inhibin production. The aim of this study was to investigate the relationship between serum inhibins A and B, FSH and estradiol in normal women between the ages of 20 and 50 years. DESIGN AND PATIENTS: Serum from 66 regularly cycling subjects, aged 20-50 years, was collected on days 3-5 of the menstrual cycle for this cross-sectional study. MEASUREMENTS: Serum inhibin A and inhibin B levels were measured by specific enzyme-linked immunosorbent assays (ELISAs). Alpha subunit forms were determined by an immunofluorometric assay which detects all known monomeric and dimeric forms of inhibin A and inhibin B and free alpha subunit. FSH and estradiol levels were measured by immunoassay. Data were log transformed before analysis. RESULTS: Serum FSH, inhibin A and estradiol, but not inhibin B, were positively correlated (p < 0.05-p < 0.001) with age between years 20 and 50. Between 40 and 50 years, serum FSH was negatively correlated with inhibin B (r = -0.61, p < 0.001) and alpha subunit forms (r = -0.47, p < 0.05) and with estradiol (r = -0.39, p < 0.05), but not with inhibin A (r = -0.21, not significant). When log(FSH) was modelled as a function of log(inhibin B) and log(estradiol) with age fitted as a covariate, inhibin B only was a significant independent predictor of FSH (beta = -0.30, p < 0.01). Using purified inhibin A and B standards for the three assays, which were calibrated in terms of their alpha subunit content, serum inhibin A levels were 10-15% of those of inhibin B, with inhibin A + B levels being 22% of total alpha subunit levels. No significant correlation was observed between total inhibin alpha subunit and its dimers. The free alpha subunit, as determined from the difference in levels of total alpha subunit and inhibin A + B, remained relatively unchanged with age, suggesting that it is not differentially regulated. CONCLUSIONS: This study shows that, during the early follicular phase, FSH, inhibin A and estradiol but not inhibin B increase with age. Some of the increase in inhibin A and estradiol may be the result of accelerated follicular development with increasing age. Serum inhibin B and estradiol but not inhibin A are inversely correlated with FSH between ages 40 and 50, but only inhibin B is a significant independent predictor of FSH. This supports the postulate that inhibin B is the main form of inhibin regulating FSH at this stage of the menstrual cycle. During the early follicular phase, serum levels of inhibin A are presumably too low to play a significant physiological role or are less active.

Adult↗
PubMed1999

Inhibin forms in serum from postmenopausal women with ovarian cancers.

BACKGROUND AND OBJECTIVE: Previous studies have shown that serum inhibin as measured by alpha subunit-directed radioimmunoassay (RIA) and inhibin A ELISA was elevated in postmenopausal women with mucinous and granulosa cell cancers, with the RIA showing a more frequent elevation than the inhibin A ELISA. It was thus hypothesised that these cancers may also produce inhibin B or the free alpha subunit. The aim of the study was to identify the forms of inhibin found in a range of ovarian cancers using a range of inhibin assays with varying specificities. DESIGN: Serum samples obtained from women with ovarian cancer were assayed by inhibin B ELISA and Pro-alpha C subunit ELISA and compared with inhibin RIA and inhibin A ELISA. PATIENTS: Blood samples were obtained from 34 postmenopausal women (> 55 years) with no history of endocrine disease and from women with ovarian serous cystadenocarcinomas (n = 66), mucinous cystadenocarcinomas (n = 20), granulosa cell tumours (n = 9-11), miscellaneous ovarian cancers (n = 46) and non ovarian cancers (n = 23). MEASUREMENTS: Inhibin B and inhibin Pro-alpha C subunit levels were determined by ELISA and compared to values obtained by RIA and inhibin A ELISA. Cancers were discriminated from controls based on values obtained 2SD above the geometric mean of the control values. RESULTS: Granulosa cell tumours were detected by RIA and inhibin B ELISA (100%), Pro-alpha C ELISA (90%) and inhibin A ELISA (77%). Mucinous tumours were detected by RIA (70%), inhibin B ELISA (60%), Pro-alpha C ELISA (55%) and inhibin A (20%). Serous tumours were detected by RIA (35%) and the other assays (< 15%). Miscellaneous tumours were detected by RIA (41%) and other assays < 30%. CONCLUSIONS: Ovarian neoplasms may produce a variety of peptides related to the inhibins, including dimeric inhibin A and B. Inhibin B is detected in more ovarian cancers than inhibin A but does not discriminate as well as the alpha subunit directed assays. The higher discrimination index obtained with the RIA compared to the Pro-alpha C ELISA suggests that assays detecting all inhibin forms containing the alpha subunit and not just those detecting the Pro-alpha C subunit will provide the most useful detection method.

Aged↗
PubMed1999

Prospectively measured levels of serum follicle-stimulating hormone, estradiol, and the dimeric inhibins during the menopausal transition in a population-based cohort of women.

The aims of this study were: 1) to describe, in relation to the date of final menses, the average hormone levels of women in the years before and after this date and to determine the extent to which these average levels were dependent on age and body mass index (BMI); and 2) to determine the degree of tracking in residual hormone levels [i.e., the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses]. Serial levels of serum FSH, circulating estradiol (E2), and the dimeric inhibins (INH) A and B were measured annually in 150 women who experienced a natural menopause during 6 years of follow-up. Means of the log-transformed hormonal levels were analyzed as a double-logistic function of time relative to FMP, as well as age and BMI and correlations between repeated hormonal levels, were measured. Mean FSH levels started to increase from about 2 years before the FMP, increased most rapidly about 10 months before the FMP, and had virtually plateaued by 2 years after the FMP. FSH levels were, on average, 3% greater for each year of age and 2% lower for each kg/m2 of BMI. After adjusting for time relative to the FMP, logFSH showed modest tracking. Age-adjusted values of logFSH were moderately correlated across time, and much of this tracking was explained by the actual timing of a woman's FMP. Mean E2 levels started to decrease about 2 years before the FMP, decreased most rapidly around the time of the FMP, and had virtually plateaued by 2 years after the FMP. E2 levels were lower, on average, by about 9% per year of age, and residual values showed weak tracking. Levels of both INHA and INHB decreased, on average, in the years before the FMP and were undetectable (INHA, < 10 pg/mL; INHB, < 25 pg/mL) in the majority of women by the time of the FMP and in almost all women by 4 years post-FMP. Significant negative correlations between log serum FSH and log E2 (r = -0.73) and log INHA (r = -0.41) and log INHB (r = -0.36) were observed. It is concluded that substantial changes in reproductive hormone levels occur within 1-2 yr on each side of the FMP, that falling concentrations of E2 and the INH contribute to the rising concentrations of FSH, and that there is no single reliable hormonal marker of menopausal status for an individual woman.

Aging↗