Differential effects of activin A on basal and gonadotrophin-induced secretion of inhibin A and progesterone by granulosa cells from preovulatory (F1-F3) chicken follicles

Previous work has shown that activin A is expressed selectively within the theca rather than the granulosa layer of preovulatory chicken follicles. In the present study, this finding was verified and the potential paracrine actions of activin A on basal and gonadotrophin-induced secretion of inhibin A, inhibin B and progesterone by granulosa cells from the three largest preovulatory follicles (F1-F3) were investigated. Treatment with activin A (0, 0.25, 2.5 and 25 ng ml(-1)) alone increased inhibin A secretion markedly in a follicle- and time-dependent manner, with the greatest response (up to 15-fold increase; P < 0.0001) in F1 follicles after 3 days of treatment. In contrast, activin A alone had no effect on progesterone output at any time. Cells from F3 follicles were more responsive to FSH than were F1 cells in terms of both inhibin A (P < 0.02) and progesterone (P < 0.01) secretion. Furthermore, activin A greatly enhanced FSH-induced secretion of both inhibin A (up to tenfold; P < 0.0001) and progesterone (up to sixfold; P < 0.0001). In terms of LH-induced inhibin A and progesterone secretion, cells from F1, F2 and F3 follicles showed similar responses. Co-treatment with activin A enhanced LH-induced secretion of inhibin A markedly (up to ninefold; P < 0.0001) but had only a marginal effect on LH-induced progesterone secretion (up to twofold; P < 0.001). The presence of activin receptor subtypes IA, IB, IIA and IIB in cultured granulosa cells from F1, F2 and F3 follicles was demonstrated using immunocytochemistry. These findings support the hypothesis that activin A secreted by the theca layers of avian preovulatory follicles exerts a local paracrine action on granulosa cells to modulate 'basal' inhibin A secretion and to upregulate gonadotrophin-induced secretion of both inhibin A and progesterone. However, the extent to which this local role of activin A contributes to the generation of the preovulatory LH-progesterone surge remains to be established.

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206. Differential regulation of activin and inhibin production by interleukin 1 (IL1), transforming growth factor β1 (TGFβ1) and protein kinase C (PKC) in the Sertoli cell and granulosa cell

Reproduction Fertility and Development ◽

10.1071/srb08abs206 ◽

2008 ◽

Vol 20 (9) ◽

pp. 6 ◽

Cited By ~ 1

Author(s):

V. Eede ◽

J. A. Muir ◽

A. E. O. 'Connor ◽

W. R. Winnall ◽

A. E. Drummond ◽

...

Keyword(s):

Mrna Expression ◽

Sertoli Cell ◽

Granulosa Cells ◽

Sertoli Cells ◽

Activin A ◽

Inhibin B ◽

Inhibin A ◽

Α Subunit ◽

Subunit Mrna ◽

Subunit Expression

Activin and inhibin are gonadal regulatory proteins comprising an α-subunit and either a βA-subunit or βB-subunit (inhibin A or B), or two βA-subunits (activin A). Synthesis of the α-subunit, and the inhibins, is regulated by FSH via cAMP/protein kinase A. Regulation of the β-subunits in the gonads is less well defined, but the IL1/MAP kinase, TGFβ /Smad and PKC pathways have been implicated. Sertoli cells and granulosa cells were isolated from 18–22 day-old Sprague-Dawley rats under standard conditions and cultured with IL1, TGFβ1 and the PKC agonists, gonadotrophin releasing hormone (GnRH) or phorbol myristate acetate (PMA). Activin A, inhibin A and inhibin B were measured in culture medium (at 48h) by ELISA. Subunit mRNA expression was measured in cell extracts (at 4 h and 8h) using quantitative RT–PCR. IL1 stimulated βA-subunit and activin A production and inhibited α-subunit and βB-subunit expression and inhibin B production in Sertoli cells, but had no effect in granulosa cells. TGFβ1 stimulated activin A in both cell types, as well as the inhibins in granulosa cells. Surprisingly, TGFβ1 had no effect on Sertoli cell α-subunit or βA-subunit mRNA expression, but did cause a slight reduction of βB-subunit expression. GnRH increased activin A and inhibin A, but not inhibin B, production by granulosa cells and had no effect on Sertoli cells, which lack the GnRH receptor. However, direct activation of PKC by PMA stimulated βA-subunit mRNA expression and activin A production and decreased βB-subunit and inhibin B production by Sertoli cells, with marginal effects on inhibin A. These results indicate that activation of the TGFβ or PKC signalling pathways preferentially stimulates βA-subunit expression and/or translation, leading to increased activin A secretion by Sertoli cells and both activin A and inhibin A secretion by granulosa cells. The ability of IL1 to stimulate activin A is confined to the Sertoli cell.

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Modulation of Amniotic Fluid Activin-A and Inhibin-A in Women With Preterm Premature Rupture of the Membranes and Infection-Induced Preterm Birth

American Journal of Reproductive Immunology ◽

10.1111/j.1600-0897.2011.01074.x ◽

2011 ◽

Vol 67 (2) ◽

pp. 122-131 ◽

Cited By ~ 14

Author(s):

Victor A. Rosenberg ◽

Irina A. Buhimschi ◽

Antonette T. Dulay ◽

Sonya S. Abdel-Razeq ◽

Emily A. Oliver ◽

...

Keyword(s):

Preterm Birth ◽

Amniotic Fluid ◽

Activin A ◽

Premature Rupture ◽

Inhibin A ◽

Preterm Premature Rupture

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Differential effects of aging on activin A and its binding protein, follistatin, across the menopause transition

Fertility and Sterility ◽

10.1016/j.fertnstert.2006.12.009 ◽

2007 ◽

Vol 88 (4) ◽

pp. 1003-1005 ◽

Cited By ~ 18

Author(s):

Nancy E. Reame ◽

Jane L. Lukacs ◽

Pamela Olton ◽

Rudi Ansbacher ◽

Vasantha Padmanabhan

Keyword(s):

Binding Protein ◽

Activin A ◽

Differential Effects ◽

Menopause Transition ◽

Effects Of Aging

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Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre-eclampsia

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.8800 ◽

2011 ◽

Vol 37 (5) ◽

pp. 528-533 ◽

Cited By ~ 45

Author(s):

J. Yu ◽

C. Z. Shixia ◽

Y. Wu ◽

T. Duan

Keyword(s):

Growth Factor ◽

Pulsatility Index ◽

Uterine Artery ◽

Activin A ◽

Placental Growth Factor ◽

Inhibin A ◽

Uterine Artery Doppler

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Inverse correlation between baseline inhibin B and FSH after stimulation with GnRH: a study of serum levels of inhibin A and B, pro alpha-C and activin A in women with ovulatory disturbances before and after stimulation with GnRH

Acta Endocrinologica ◽

10.1530/eje.0.1430077 ◽

2000 ◽

pp. 77-84 ◽

Cited By ~ 2

Author(s):

FW Casper ◽

RJ Seufert ◽

K Pollow

Keyword(s):

Inverse Correlation ◽

Strong Relationship ◽

Serum Levels ◽

Activin A ◽

Inhibin B ◽

Inhibin A ◽

Before And After ◽

Pituitary Secretion ◽

Objective Interest ◽

A Minor

OBJECTIVE: Interest has focused recently on the influences of the polypeptide factors inhibin and activin on the selective regulation of the pituitary secretion of gonadotropins. DESIGN: Measurement of the concentrations of inhibin-related proteins in relation to the changes in pituitary gonadotropin (FSH, LH) parameters, after GnRH stimulation with a bolus injection of 100 microg gonadorelin, in 19 women with ovulatory disturbances. METHODS: Serum levels of inhibin A and B, activin A, and pro alpha-C were measured using sensitive ELISA kits. RESULTS: Within 60 min after GnRH stimulation, FSH values doubled from 5 to 10 mU/ml (P < 0.001). LH increased 12-fold from 2 to 24 mU/ml (P < 0.001). Activin A showed a significant decrease from 0.47 to 0.36 ng/ml (P < 0.001), whereas pro alpha-C increased from 127 to 156 pg/ml (P = 0.039). The median inhibin A concentration did not show a significant change between baseline and the 60 min value, whereas inhibin B was characterized by a minor, but not significant, increase in the median from 168 to 179 pg/ml (P = 0.408). A significant inverse correlation (P = 0.014) with a mean coefficient of correlation of 0.5516 was found, demonstrating a strong relationship between high inhibin B baseline levels and a small increase of FSH after 60 min. CONCLUSION: Our results show an interesting correlation between the baseline inhibin B and the change in FSH before and after GnRH stimulation. A high baseline inhibin B implies only a minor increase of FSH after 60 min.

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Pregnancy-associated and placental proteins in the placental tissue of normal pregnant women and patients with pre-eclampsia at term

Acta Endocrinologica ◽

10.1530/eje.0.1470785 ◽

2002 ◽

pp. 785-793 ◽

Cited By ~ 35

Author(s):

NA Bersinger ◽

N Groome ◽

S Muttukrishna

Keyword(s):

Pregnant Women ◽

Protein A ◽

Placental Tissue ◽

Serum Levels ◽

Activin A ◽

Placental Lactogen ◽

Compensatory Mechanism ◽

Protein Markers ◽

Inhibin A ◽

Placental Disease

OBJECTIVE: Pre-eclampsia is a placental disease of unknown cause. Maternal circulating concentrations of a number of protein markers are altered (mainly increased) in pre-eclampsia in comparison with controls of matched gestational age. Inhibin A and activin A were found to be elevated even before the onset of the disease. The aim of this study was to compare the levels of inhibin A, activin A: follistatin ratio, leptin, pregnancy-associated plasma protein-A (PAPP-A), human placental lactogen (HPL), placenta growth factor (PLGF) and pregnancy-specific beta1-glycoprotein (SP1) in placental extracts of normal pregnant women and pre-eclampsia patients at term. METHODS: Placental tissue from normal pregnancies (n=14) and patients with pre-eclampsia (n=13) were collected at term (> or =37 weeks of gestation) and stored at -80 degrees C. The frozen tissue pieces were homogenised and the above-mentioned proteins were measured by specific enzyme-linked immunosorbent assays. RESULTS: Placental contents of inhibin A and PAPP-A were significantly higher (P<0.05) in pre-eclampsia placental extracts compared with the controls. Activin A:follistatin ratio was higher (23) in pre-eclampsia extracts than in the controls (15). Leptin, PLGF, SP1 and HPL levels were not altered in the term pre-eclampsia placenta. Inhibin A and PAPP-A contents were increased in the placental extracts of pre-eclampsia patients. CONCLUSION: Our data suggest that the placenta, possibly by a compensatory mechanism, is at least in part responsible for the altered serum levels observed in pre-eclampsia.

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