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Semin Reprod Med 2004; 22(3): 243-252
DOI: 10.1055/s-2004-831900
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Animal Models of Inhibin Action

Ann E. Drummond1 , Jock K. Findlay1 , James J. Ireland2
  • 1Prince Henry’s Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia
  • 2Department of Animal Science, Michigan State University, East Lansing, Michigan
Further Information

Publication History

Publication Date:
20 August 2004 (online)

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The physiology of inhibin has been investigated using rodent and ruminant animal models in both in vitro and in vivo studies. Inhibin was originally defined as a substance that causes selective suppression of follicle-stimulating hormone (FSH) secretion by pituitary gonadotropes. Although this definition is still valid, it fails to encompass the breadth of inhibin's actions. In addition to its endocrine action on pituitary FSH secretion, inhibin has a local paracrine action in its target tissues. The inhibin α subunit appears to play an important role in determining whether inhibin or activin is produced in cells. More recently, transgenic and knockout mouse models have highlighted the importance of inhibin for fertility and the inhibin α subunit for tumor suppression. Whether inhibin exerts its effects by a direct action on the gonad or by regulating FSH secretion, it is clear that inhibin is essential for normal reproductive function. In this article, we review the rodent and ruminant models employed to investigate inhibin physiology and examine the potential of inhibin-based vaccines to enhance gonadal function.

KEYWORDS

Inhibin - rodents - ruminants - models - veterinary

REFERENCES

  • 1 Scott R S, Burger H G, Quigg H. A simple and rapid in vitro bioassay for inhibin.  Endocrinology. 1980;  107 1536-1542
    PubMedGoogle Scholar
  • 2 Schwartz N B, Channing C P. Evidence for ovarian “inhibin” suppression of he secondary rise in serum follicle stimulating hormone levels in proestrus rats by injection of porcine follicular.  Proc Natl Acad Sci USA. 1977;  74 5721-5724
    PubMedGoogle Scholar
  • 3 DeJong F, Sharpe R M. Evidence for inhibin-like activity in bovine follicular fluid.  Nature. 1976;  263 71-72
    PubMedGoogle Scholar
  • 4 D'Agostino J, Woodruff T K, Mayo K E, Schwartz N B. Unilateral ovariectomy increases inhibin messenger ribonucleic acid levels in newly recruited follicles.  Endocrinology. 1989;  124 310-317
    PubMedGoogle Scholar
  • 5 Woodruff T K, D'Agostino J, Schwartz N B, Mayo K E. Dynamic changes in inhibin messenger RNAs in rat ovarian follicles during the reproductive cycle.  Science. 1988;  239 1296-1299
    PubMedGoogle Scholar
  • 6 Smyth C D, Gosden R G, McNeilly A S, Hillier S G. Effect of inhibin immunoneutralization on steroidogenesis in rat ovarian follicles in vitro.  J Endocrinol. 1994;  140 437-443
    PubMedGoogle Scholar
  • 7 Hsueh A J, Dahl K D, Vaughan J et al.. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis.  Proc Natl Acad Sci USA. 1987;  84 5082-5086
    PubMedGoogle Scholar
  • 8 Hillier S G, Yong E L, Illingworth P J, Baird D T, Schwall R H, Mason A J. Effect of recombinant inhibin on androgen synthesis in cultured human thecal cells.  Mol Cell Endocrinol. 1991;  75 R1-R6
    CrossrefPubMedGoogle Scholar
  • 9 Rivier C, Vale W. Immunoneutralization of endogenous inhibin modifies hormone secretion and ovulation rate in the rat.  Endocrinology. 1989;  125 152-157
    PubMedGoogle Scholar
  • 10 Culler M D, Negro-Vilar A. Passive immunoneutralization of endogenous inhibin: sex-related differences in the role of inhibin during development.  Mol Cell Endocrinol. 1988;  58 263-273
    CrossrefPubMedGoogle Scholar
  • 11 Culler M D, Negro-Vilar A. Endogenous inhibin suppresses only basal follicle-stimulating hormone secretion but suppresses all parameters of pulsatile luteinizing hormone secretion in the diestrous female rat.  Endocrinology. 1989;  124 2944-2953
    PubMedGoogle Scholar
  • 12 Vanage G R, Mehta P B, Moodbidri S B, Iyer K S. Effect of immunization with synthetic peptide corresponding to region 1-17 of human seminal plasma inhibin on fertility of male rats.  Arch Androl. 2000;  44 11-21
    PubMedGoogle Scholar
  • 13 Matzuk M M, Finegold M J, Su J G, Hsueh A J, Bradley A. Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice.  Nature. 1992;  360 313-319
    CrossrefPubMedGoogle Scholar
  • 14 Matzuk M M, Finegold M J, Mather J P, Krummen L, Lu H, Bradley A. Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice.  Proc Natl Acad Sci USA. 1994;  91 8817-8821
    PubMedGoogle Scholar
  • 15 Pierson T M, Wang Y, DeMayo F J, Matzuk M M, Tsai S Y, Omalley B W. Regulable expression of inhibin A in wild-type and inhibin alpha null mice.  Mol Endocrinol. 2000;  14 1075-1085
    CrossrefPubMedGoogle Scholar
  • 16 McMullen M L, Cho B N, Yates C J, Mayo K E. Gonadal pathologies in transgenic mice expressing the rat inhibin alpha-subunit.  Endocrinology. 2001;  142 5005-5014
    CrossrefPubMedGoogle Scholar
  • 17 Cho B N, McMullen M L, Pei L, Yates C J, Mayo K E. Reproductive deficiencies in transgenic mice expressing the rat inhibin alpha-subunit gene.  Endocrinology. 2001;  142 4994-5004
    CrossrefPubMedGoogle Scholar
  • 18 Ling N, Ying S Y, Ueno N, Esch F, Denoroy L, Guillemin R. Isolation and partial characterization of a Mr 32,000 protein with inhibin activity from porcine follicular fluid.  Proc Natl Acad Sci USA. 1985;  82 7217-7221
    PubMedGoogle Scholar
  • 19 Vale W, Rivier J, Vaughan J et al.. Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid.  Nature. 1986;  321 776-779
    CrossrefPubMedGoogle Scholar
  • 20 Robertson D M, Tsonis C G, McLachlan R I et al.. Comparison of inhibin immunological and in vitro biological activities in human serum.  J Clin Endocrinol Metab. 1988;  67 438-443
    PubMedGoogle Scholar
  • 21 Baker H WG, Eddie L W, Higginson R E, Hudson B, Niall H D. Clinical context, neuro-endocrine relationships and nature of inhibin in males and females. In: Martini GMBL Clinical Neuroendocrinology New York; Academic Press 1982: 283-330
    Google Scholar
  • 22 Robertson D M, Foulds L M, Leversha L et al.. Isolation of inhibin from bovine follicular fluid.  Biochem Biophys Res Commun. 1985;  126 220-226
    CrossrefPubMedGoogle Scholar
  • 23 Leversha L, Robertson D M, de Vos F L et al.. Isolation and purification of ovine inhibin. Proceedings of the Endocrine Society of Australia Brisbane, Abstract, 1986
    Google Scholar
  • 24 Forage R G, Ring J M, Brown R W et al.. Cloning and sequence analysis of cDNA species coding for the two subunits of inhibin from bovine follicular fluid.  Proc Natl Acad Sci USA. 1986;  83 3091-3095
    PubMedGoogle Scholar
  • 25 Mason A J, Hayflick J S, Ling N et al.. Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth factor-beta.  Nature. 1985;  318 659-663
    CrossrefPubMedGoogle Scholar
  • 26 Findlay J K, Clarke I J. Regulation of the secretion of FSH in domestic ruminants.  J Reprod Fertil Suppl. 1987;  34 27-37
    PubMedGoogle Scholar
  • 27 Taya K, Kaneko H, Watanabe G, Sasamoto S. Inhibin and secretion of FSH in oestrous cycles of cows and pigs.  J Reprod Fertil Suppl. 1991;  43 151-162
    PubMedGoogle Scholar
  • 28 Findlay J K, Robertson D M, Clarke I J. Influence of dose and route of administration of bovine follicular fluid and the suppressive effect of purified bovine inhibin (Mr 31,000) on plasma FSH concentrations in ovariectomized ewes.  J Reprod Fertil. 1987;  80 455-461
    PubMedGoogle Scholar
  • 29 Clarke I J, Tilbrook A J, Galloway D B, Earl C R, Findlay J K, de Kretser D M. Inhibin in rams.  J Reprod Fertil Suppl. 1991;  43 163-170
    PubMedGoogle Scholar
  • 30 Tilbrook A J, de Kretser D M, Clarke I J. A role for inhibin in the regulation of the secretion of follicle stimulating hormone in male domestic animals.  Domest Anim Endocrinol. 1992;  9 243-260
    CrossrefPubMedGoogle Scholar
  • 31 Findlay J K. An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis.  Biol Reprod. 1993;  48 15-23
    PubMedGoogle Scholar
  • 32 Knight P G. Roles of inhibins, activins, and follistatin in the female reproductive system.  Front Neuroendocrinol. 1996;  17 476-509
    PubMedGoogle Scholar
  • 33 Kumar T R, Palapattu G, Wang P et al.. Transgenic models to study gonadotropin function: the role of follicle-stimulating hormone in gonadal growth and tumorigenesis.  Mol Endocrinol. 1999;  13 851-865
    CrossrefPubMedGoogle Scholar
  • 34 Ying S Y, Becker A, Ling N, Ueno N, Guillemin R. Inhibin and beta type transforming growth factor (TGF beta) have opposite modulating effects on the follicle stimulating hormone (FSH)-induced aromatase activity of cultured rat granulosa cells.  Biochem Biophys Res Commun. 1986;  136 969-975
    CrossrefPubMedGoogle Scholar
  • 35 Jimenez-Krassel F, Winn M E, Burns D, Ireland J L, Ireland J J. Evidence for a negative intrafollicular role for inhibin in regulation of estradiol production by granulosa cells.  Endocrinology. 2003;  144 1876-1886
    CrossrefPubMedGoogle Scholar
  • 36 Schneyer A L, Sluss P M, Whitcomb R W, Martin K A, Sprengel R, Crowley Jr W F. Precursors of alpha-inhibin modulate follicle-stimulating hormone receptor binding and biological activity.  Endocrinology. 1991;  129 1987-1999
    PubMedGoogle Scholar
  • 37 Woodruff T K, Krummen L, Chen S A et al.. Pharmacokinetic profile of recombinant human (rh) inhibin A and activin A in the immature rat. II. Tissue distribution of [125I]rh-inhibin A and [125I]rh-activin A in immature female and male rats.  Endocrinology. 1993;  132 725-734
    CrossrefPubMedGoogle Scholar
  • 38 Martens J W, de Winter J P, Timmerman M A et al.. Inhibin interferes with activin signaling at the level of the activin receptor complex in Chinese hamster ovary cells.  Endocrinology. 1997;  138 2928-2936
    CrossrefPubMedGoogle Scholar
  • 39 Tsafriri A, Vale W, Hsueh A J. Effects of transforming growth factors and inhibin-related proteins on rat preovulatory graafian follicles in vitro.  Endocrinology. 1989;  125 1857-1862
    PubMedGoogle Scholar
  • 40 O W S, Robertson D M, de Kretser D M. Inhibin as an oocyte meiotic inhibitor.  Mol Cell Endocrinol. 1989;  62 307-311
    CrossrefPubMedGoogle Scholar
  • 41 Silva C C, Groome N P, Knight P G. Demonstration of a suppressive effect of inhibin alpha-subunit on the developmental competence of in vitro matured bovine oocytes.  J Reprod Fertil. 1999;  115 381-388
    PubMedGoogle Scholar
  • 42 Hakovirta H, Kaipia A, Soder O, Parvinen M. Effects of activin-A, inhibin-A, and transforming growth factor-beta 1 on stage-specific deoxyribonucleic acid synthesis during rat seminiferous epithelial cycle.  Endocrinology. 1993;  133 1664-1668
    CrossrefPubMedGoogle Scholar
  • 43 O'Shea T, Hillier M A, Anderson S T et al.. Inhibin immunization for increasing ovulation rate and superovulation.  Theriogenology. 1994;  41 3-17
    PubMedGoogle Scholar
  • 44 Bindon B M, Anderson S T, Cummins L J et al.. Manipulation of Reproduction of Sheep and Cattle by Vaccination against Inhibin-Related Peptides. Melbourne; CSIRO Publications 1994
    Google Scholar
  • 45 Miyamoto K, Hasegawa Y, Fukuda M, Igarashi M. Demonstration of high molecular weight forms of inhibin in bovine follicular fluid (bFF) by using monoclonal antibodies to bFF 32K inhibin.  Biochem Biophys Res Commun. 1986;  136 1103-1109
    CrossrefPubMedGoogle Scholar
  • 46 Robertson D M, Giacometti M, Foulds L M et al.. Isolation of inhibin alpha-subunit precursor proteins from bovine follicular fluid.  Endocrinology. 1989;  125 2141-2149
    PubMedGoogle Scholar
  • 47 Sugino K, Nakamura T, Takio K et al.. Inhibin alpha-subunit monomer is present in bovine follicular fluid.  Biochem Biophys Res Commun. 1989;  159 1323-1329
    CrossrefPubMedGoogle Scholar
  • 48 Knight P G, Beard A J, Wrathall J H, Castillo R J. Evidence that the bovine ovary secretes large amounts of monomeric inhibin alpha subunit and its isolation from bovine follicular fluid.  J Mol Endocrinol. 1989;  2 189-200
    PubMedGoogle Scholar
  • 49 Sugino K, Nakamura T, Takio K et al.. Purification and characterization of high molecular weight forms of inhibin from bovine follicular fluid.  Endocrinology. 1992;  130 789-796
    CrossrefPubMedGoogle Scholar
  • 50 Ireland J L, Good T E, Knight P G, Ireland J J. Alterations in amounts of different forms of inhibin during follicular atresia.  Biol Reprod. 1994;  50 1265-1276
    PubMedGoogle Scholar
  • 51 Good T E, Weber P S, Ireland J L et al.. Isolation of nine different biologically and immunologically active molecular variants of bovine follicular inhibin.  Biol Reprod. 1995;  53 1478-1488
    PubMedGoogle Scholar
  • 52 Guthrie H D, Ireland J L, Good T E, Ireland J J. Expression of different molecular mass forms of inhibin in atretic and nonatretic follicles during the early luteal phase and altrenogest-synchronized follicular phase in pigs.  Biol Reprod. 1997;  56 870-877
    PubMedGoogle Scholar
  • 53 Mason A J, Farnworth P G, Sullivan J. Characterization and determination of the biological activities of noncleavable high molecular weight forms of inhibin A and activin A.  Mol Endocrinol. 1996;  10 1055-1065
    CrossrefPubMedGoogle Scholar
  • 54 Robertson D M, Foulds L M, Prisk M, Hedger M P. Inhibin/activin beta-subunit monomer: isolation and characterization.  Endocrinology. 1992;  130 1680-1687
    CrossrefPubMedGoogle Scholar
  • 55 Souza C J, Campbell B K, Webb R, Baird D T. Secretion of inhibin A and follicular dynamics throughout the estrous cycle in the sheep with and without the Booroola gene (FecB).  Endocrinology. 1997;  138 5333-5340
    CrossrefPubMedGoogle Scholar
  • 56 Knight P G, Feist S A, Tannetta D S et al.. Measurement of inhibin-A (alpha beta A dimer) during the oestrous cycle, after manipulation of ovarian activity and during pregnancy in ewes.  J Reprod Fertil. 1998;  113 159-166
    PubMedGoogle Scholar
  • 57 Bleach E C, Glencross R G, Feist S A, Groome N P, Knight P G. Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid.  Biol Reprod. 2001;  64 743-752
    PubMedGoogle Scholar
  • 58 Kaneko H, Noguchi J, Kikuchi K, Todoroki J, Hasegawa Y. Alterations in peripheral concentrations of inhibin A in cattle studied using a time-resolved immunofluorometric assay: relationship with estradiol and follicle-stimulating hormone in various reproductive conditions.  Biol Reprod. 2002;  67 38-45
    PubMedGoogle Scholar
  • 59 Mihm M, Good T E, Ireland J L, Ireland J J, Knight P G, Roche J F. Decline in serum follicle-stimulating hormone concentrations alters key intrafollicular growth factors involved in selection of the dominant follicle in heifers.  Biol Reprod. 1997;  57 1328-1337
    PubMedGoogle Scholar
  • 60 Mihm M, Austin E J, Good T E et al.. Identification of potential intrafollicular factors involved in selection of dominant follicles in heifers.  Biol Reprod. 2000;  63 811-819
    PubMedGoogle Scholar
  • 61 Schneyer A L, Fujiwara T, Fox J et al.. Dynamic changes in the intrafollicular inhibin/activin/follistatin axis during human follicular development: relationship to circulating hormone concentrations.  J Clin Endocrinol Metab. 2000;  85 3319-3330
    CrossrefPubMedGoogle Scholar
  • 62 Groome N P, Illingworth P J, O'Brien M et al.. Measurement of dimeric inhibin B throughout the human menstrual cycle.  J Clin Endocrinol Metab. 1996;  81 1401-1405
    CrossrefPubMedGoogle Scholar
  • 63 Woodruff T K, Besecke L M, Groome N, Draper L B, Schwartz N B, Weiss J. Inhibin A and inhibin B are inversely correlated to follicle-stimulating hormone, yet are discordant during the follicular phase of the rat estrous cycle, and inhibin A is expressed in a sexually dimorphic manner.  Endocrinology. 1996;  137 5463-5467
    CrossrefPubMedGoogle Scholar
  • 64 Forage R G, Brown R W, Oliver K J et al.. Immunization against an inhibin subunit produced by recombinant DNA techniques results in increased ovulation rate in sheep.  J Endocrinol. 1987;  114 R1-R4
    PubMedGoogle Scholar
  • 65 McLeod B J, Hunter M G, Bleach E C, Glencross R G, Wrathall J H. Preovulatory follicle development and luteal function in ewes immunized against a synthetic peptide sequence of the alpha subunit of bovine inhibin.  J Endocrinol. 1992;  133 413-419
    PubMedGoogle Scholar
  • 66 D'Alessandro A, Martemucci G, Iaffaldano N. Active immunization with a synthetic fragment of pig inhibin alpha-subunit increases ovulation rate and embryo production in superovulated ewes but season affects its efficiency.  J Reprod Fertil. 1999;  115 185-191
    PubMedGoogle Scholar
  • 67 Morris D G, McDermott M G, Diskin M G, Morrison C A, Swift P J, Sreenan J M. Effect of immunization against synthetic peptide sequences of bovine inhibin alpha-subunit on ovulation rate and twin-calving rate in heifers.  J Reprod Fertil. 1993;  97 255-261
    PubMedGoogle Scholar
  • 68 Scanlon A R, Sunderland S J, Martin T L et al.. Active immunization of heifers against a synthetic fragment of bovine inhibin.  J Reprod Fertil. 1993;  97 213-222
    PubMedGoogle Scholar
  • 69 Morris D G, McDermott M G, Grealy M et al.. Effect of immunization against synthetic peptide sequences of the alpha N-subunit of bovine inhibin on ovulation rate, gonadotrophin concentrations and fertility in heifers.  J Reprod Fertil. 1995;  103 285-291
    PubMedGoogle Scholar
  • 70 Hillard M A, Wilkins J F, Cummins L J et al.. Immunological manipulation of ovulation rate for twinning in cattle.  J Reprod Fertil Suppl. 1995;  49 351-364
    PubMedGoogle Scholar
  • 71 Brown R W, Hungerford J W, Greenwood P E et al.. Immunization against recombinant bovine inhibin alpha subunit causes increased ovulation rates in gilts.  J Reprod Fertil. 1990;  90 199-205
    PubMedGoogle Scholar
  • 72 Ahn J, You S, Kim H, Chaiseha Y, El Halawani M. Effects of active immunization with inhibin alpha subunit on reproductive characteristics of turkey hens.  Biol Reprod. 2001;  65 1594-1600
    PubMedGoogle Scholar
  • 73 Satterlee D G, Cadd G G, Fioretti W C. Active immunization of broiler breeder hens with a recombinant chicken inhibin fusion protein enhances egg lay.  Poult Sci. 2002;  81 519-528
    PubMedGoogle Scholar
  • 74 McKinnon A O, Brown R W, Pashen R L, Greenwood P E, Vasey J R. Increased ovulation rates in mares after immunisation against recombinant bovine inhibin alpha-subunit.  Equine Vet J. 1992;  24 144-146
    PubMedGoogle Scholar
  • 75 Russell D L, Salamonsen L A, Findlay J K. Immunization against the N-terminal peptide of the inhibin alpha 43-subunit (alpha N) disrupts tissue remodeling and the increase in matrix metalloproteinase-2 during ovulation.  Endocrinology. 1995;  136 3657-3664
    CrossrefPubMedGoogle Scholar
  • 76 Dhar A, Salamonsen L A, Doughton B W, Brown R W, Findlay J K. Effect of immunization against the amino-terminal peptide (alpha N) of the alpha 43-subunit of inhibin on follicular atresia and expression of tissue inhibitor of matrix metalloproteinase (TIMP-1) in ovarian follicles of sheep.  J Reprod Fertil. 1998;  114 147-155
    PubMedGoogle Scholar
  • 77 Mizumachi M, Voglmayr J K, Washington D W, Chen C L, Bardin C W. Superovulation of ewes immunized against the human recombinant inhibin alpha-subunit associated with increased pre- and postovulatory follicle-stimulating hormone levels.  Endocrinology. 1990;  126 1058-1063
    PubMedGoogle Scholar
  • 78 Schanbacher B D, Schemm S R, Rhind S M. Gonadotrophin concentrations and ovulation rates in Suffolk ewes actively or passively immunized against inhibin alpha.  J Reprod Fertil. 1991;  93 133-139
    PubMedGoogle Scholar
  • 79 Wheaton J E, Carlson K M, Kusina N T. Active and passive immunoneutralization of inhibin increases follicle-stimulating hormone levels and ovulation rate in ewes.  Biol Reprod. 1992;  47 361-367
    PubMedGoogle Scholar
  • 80 Wrathall J H, McLeod B J, Glencross R G, Knight P G. Effects of active immunization against a synthetic peptide sequence of the inhibin alpha-subunit on plasma gonadotrophin concentrations, ovulation rate and lambing rate in ewes.  J Reprod Fertil. 1992;  95 175-182
    PubMedGoogle Scholar
  • 81 Mann G E, Campbell B K, McNeilly A S, Baird D T. Follicular development and ovarian hormone secretion following passive immunization of ewes against inhibin or oestradiol.  J Endocrinol. 1993;  136 225-233
    PubMedGoogle Scholar
  • 82 Russell D L, Doughton B W, Tsonis C G, Findlay J K. Pituitary and ovarian function in ewes immunized against the amino-terminal peptide (alpha N) of the inhibin alpha 43-subunit.  J Reprod Fertil. 1994;  100 115-122
    PubMedGoogle Scholar
  • 83 Kusina N T, Meyer R L, Carlson K M, Wheaton J E. Effects of passive immunization of ewes against an inhibin-peptide on gonadotropin levels, ovulation rate, and prolificacy.  Biol Reprod. 1995;  52 878-884
    PubMedGoogle Scholar
  • 84 Wheaton J E, Thomas D L, Kusina N T, Gottfredson R G, Meyer R L. Effects of passive immunization against inhibin-peptide on secretion of follicle-stimulating hormone and ovulation rate in ewes carrying the Booroola fecundity gene.  Biol Reprod. 1996;  55 1351-1355
    PubMedGoogle Scholar
  • 85 Anderson S T, Bindon B M, Hillard M A, O'Shea T. Increased ovulation rate in Merino ewes immunized against small synthetic peptide fragments of the inhibin alpha subunit.  Reprod Fertil Dev. 1998;  10 421-431
    PubMedGoogle Scholar
  • 86 Voglmayr J K, Mizumachi M, Washington D W, Chen C L, Bardin C W. Immunization of rams against human recombinant inhibin alpha-subunit delays, augments, and extends season-related increase in blood gonadotropin levels.  Biol Reprod. 1990;  42 81-86
    PubMedGoogle Scholar
  • 87 McKeown R M, O'Callaghan D, Roche J F, Boland M P. Effect of immunization of rams against bovine inhibin alpha 1-26 on semen characteristics, scrotal size, FSH, LH and testosterone concentrations.  J Reprod Fertil. 1997;  109 237-245
    PubMedGoogle Scholar
  • 88 Kaneko H, Nakanishi Y, Taya K et al.. Evidence that inhibin is an important factor in the regulation of FSH secretion during the mid-luteal phase in cows.  J Endocrinol. 1993;  136 35-41
    PubMedGoogle Scholar
  • 89 Glencross R G, Bleach E C, Wood S C, Knight P G. Active immunization of heifers against inhibin: effects on plasma concentrations of gonadotrophins, steroids and ovarian follicular dynamics during prostaglandin-synchronized cycles.  J Reprod Fertil. 1994;  100 599-605
    PubMedGoogle Scholar
  • 90 Kaneko H, Nakanishi Y, Akagi S et al.. Immunoneutralization of inhibin and estradiol during the follicular phase of the estrous cycle in cows.  Biol Reprod. 1995;  53 931-939
    PubMedGoogle Scholar
  • 91 Akagi S, Kaneko H, Nakanishi Y, Takedomi T, Watanabe G, Taya K. Ovarian response and FSH profile in cows following injection of various doses of inhibin antiserum.  J Vet Med Sci. 1997;  59 1129-1135
    CrossrefPubMedGoogle Scholar
  • 92 Martin T L, Williams G L, Lunstra D D, Ireland J J. Immunoneutralization of inhibin modifies hormone secretion and sperm production in bulls.  Biol Reprod. 1991;  45 73-77
    PubMedGoogle Scholar
  • 93 Bame J H, Dalton J C, Degelos S D et al.. Effect of long-term immunization against inhibin on sperm output in bulls.  Biol Reprod. 1999;  60 1360-1366
    PubMedGoogle Scholar
  • 94 King B F, Britt J H, Esbenshade K L et al.. Ovulatory and endocrine responses after active immunization of gilts against a synthetic fragment of bovine inhibin.  J Anim Sci. 1993;  71 975-982
    PubMedGoogle Scholar
  • 95 Medan M S, Watanabe G, Sasaki K et al.. Ovarian and hormonal response of female goats to active immunization against inhibin.  J Endocrinol. 2003;  177 287-294
    CrossrefPubMedGoogle Scholar
  • 96 Medan M S, Watanabe G, Sasaki K et al.. Effects of passive immunization of goats against inhibin on follicular development, hormone profile and ovulation rate.  Reproduction. 2003;  125 751-757
    CrossrefPubMedGoogle Scholar
  • 97 Moreau J D, Satterlee D G, Rejman J J, Cadd G G, Kousoulas K G, Fioretti W C. Active immunization of Japanese quail hens with a recombinant chicken inhibin fusion protein enhances production performance.  Poult Sci. 1998;  77 894-901
    PubMedGoogle Scholar
  • 98 Nambo Y, Kaneko H, Nagata S et al.. Effect of passive immunization against inhibin on FSH secretion, folliculogenesis and ovulation rate during the follicular phase of the estrous cycle in mares.  Theriogenology. 1998;  50 545-557
    CrossrefPubMedGoogle Scholar
  • 99 Schanbacher B D. Pituitary and testicular responses of beef bulls to active immunization against inhibin alpha.  J Anim Sci. 1991;  69 252-257
    PubMedGoogle Scholar
  • 100 Wheaton J E, Meyer R L, Jones R H, Kramer A J. Effects of passive immunization using antibody against an alpha-inhibin peptide on follicle-stimulating hormone concentrations and litter size in sows.  Theriogenology. 1998;  49 813-822
    CrossrefPubMedGoogle Scholar
  • 101 Findlay J K, Tsonis C G, Doughton B et al.. Immunisation against the amino-terminal peptide (alpha N) of the alpha 43 subunit of inhibin impairs fertility in sheep.  Endocrinology. 1989;  124 3122-3124
    PubMedGoogle Scholar
  • 102 Dhar A, Doughton B W, Pruysers E, Brown R W, Findlay J K. Effect of immunization against the alpha N (alphaN) and alpha C (alphaC) peptides of the alpha43 subunit of inhibin on antral follicular growth and atresia and the patterns of gonadotrophin secretion in ewes.  Reproduction. 2001;  121 707-718
    CrossrefPubMedGoogle Scholar
  • 103 Ireland J J, Martin T L, Ireland J L, Aulerich R J. Immunoneutralization of inhibin suppresses reproduction in female mink.  Biol Reprod. 1992;  47 746-750
    PubMedGoogle Scholar
  • 104 Wrathall J H, McLeod B J, Glencross R G, Beard A J, Knight P G. Inhibin immunoneutralization by antibodies raised against synthetic peptide sequences of inhibin alpha subunit: effects on gonadotrophin concentrations and ovulation rate in sheep.  J Endocrinol. 1990;  124 167-176
    PubMedGoogle Scholar
  • 105 Meyer R L, Carlson K M, Rivier J, Wheaton J E. Antiserum to an inhibin alpha-chain peptide neutralizes inhibin bioactivity and increases ovulation rate in sheep.  J Anim Sci. 1991;  69 747-754
    PubMedGoogle Scholar
  • 106 O'Shea T, Andrews C M, Bindon B M, Hillard M A, Miyamoto K, Sinosich M J. Immunization of merino ewes with a synthetic inhibin peptide or with preparations obtained from bovine and porcine follicular fluids by immunoaffinity chromatography result in different effects on ovulation rate and on plasma gonadotrophin concentrations.  Reprod Fertil Dev. 1991;  3 659-670
    PubMedGoogle Scholar
  • 107 O'Shea T, Bindon B M, Forage R G, Findlay J K, Tsonis C G. Active immunization of Merino ewe lambs with recombinant bovine alpha inhibin advances puberty and increases ovulation rate.  Reprod Fertil Dev. 1993;  5 173-180
    PubMedGoogle Scholar
  • 108 Fray M D, Wrathall J H, Knight P G. Active immunisation against inhibin promotes a recurrent increase in litter size in sheep.  Vet Rec. 1994;  134 19-20
    PubMedGoogle Scholar
  • 109 Wheaton J E, Godfrey R W. Plasma LH, FSH, testosterone, and age at puberty in ram lambs actively immunized against an inhibin alpha-subunit peptide.  Theriogenology. 2003;  60 933-941
    CrossrefPubMedGoogle Scholar
  • 110 Glencross R G, Bleach E C, McLeod B J, Beard A J, Knight P G. Effect of active immunization of heifers against inhibin on plasma FSH concentrations, ovarian follicular development and ovulation rate.  J Endocrinol. 1992;  134 11-18
    PubMedGoogle Scholar
  • 111 Lovell T M, Knight P G, Groome N P, Gladwell R T. Changes in plasma inhibin A levels during sexual maturation in the female chicken and the effects of active immunization against inhibin alpha-subunit on reproductive hormone profiles and ovarian function.  Biol Reprod. 2001;  64 188-196
    PubMedGoogle Scholar
  • 112 Lovell T M, Knight P G, Groome N P, Gladwell R T. Measurement of dimeric inhibins and effects of active immunization against inhibin alpha-subunit on plasma hormones and testis morphology in the developing cockerel.  Biol Reprod. 2000;  63 213-221
    PubMedGoogle Scholar
  • 113 McCue P M, Carney N, Hughes J, Rivier J, Vale W, Lasley B. Ovulation and embryo recovery rates following immunization of mares against an inhibin alpha-subunit fragment.  Theriogenology. 1992;  38 823-831
    CrossrefPubMedGoogle Scholar
  • 114 Terhaar H J, Schlote S, Hoppen H O et al.. Active immunization of mares against recombinant human inhibin alpha-subunit.  Reproduction in Domestic Animals. 1997;  32 243-250
    PubMedGoogle Scholar
  • 115 King B F, Britt J H, Esbenshade K L, Flowers W L, Ireland J J. Evidence for a local role of inhibin or inhibin alpha subunits in compensatory ovarian hypertrophy.  J Reprod Fertil. 1995;  104 291-295
    PubMedGoogle Scholar

Jock K FindlayPh.D. D.Sc. 

Prince Henry's Institute of Medical Research

Level 4, Block E, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia