Hypothalamic involvement and the role of progesterone in the NGF-induced LH surge pathway

in Reproduction
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  • 1 Department of Veterinary Biomedical Sciences, Western college of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Correspondence should be addressed to G P Adams; Email: gregg.adams@usask.ca
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To elucidate the mechanism by which nerve growth factor (NGF) influences the LH secretory pathway in camelids, a series of experiments were done to determine the involvement of the hypothalamus (Experiment 1), the role of GnRH neurons (Experiment 2), and the effect of progesterone (Experiment 3) on the NGF-induced LH surge and ovulation in llamas. In Experiment 1, the declining phase of the NGF-induced LH surge was used to determine if the decline is a result of pituitary depletion or hypothalamic unresponsiveness. Female llamas were treated with NGF and, 7 h later, assigned to three groups and given a second dose of NGF (n = 5), a dose of GnRH (n = 5), or saline (n = 6). The LH response was attenuated after the second dose of NGF vs GnRH. In Experiment 2, Fos expression (marker of neuronal activation) in GnRH neurons was examined in the hypothalamus of llamas after NGF or saline treatment (n = 3 per group). Despite an LH surge in the NGF group but not in the saline group, no differences were detected between groups in Fos/GnRH co-expression. In Experiment 3, llamas in low-, medium-, and high-plasma progesterone groups (n = 4 per group) were treated with NGF. The NGF-induced LH surge did not differ among treatment groups. Results from the present study show that the induction of a preovulatory LH surge by NGF may be controlled by a novel pathway involving GnRH neuro-terminals downstream of the hypothalamus and is independent of progesterone influence.

Supplementary Materials

    • Supplementary Figure 1. Experiment 3: Effect of progesterone on GnRH-induced LH release in llamas. Llamas were pre-treated with long-acting progesterone (P4-GnRH, n = 4) or left untreated (n = 4) before GnRH treatment. Arrow indicates time of treatment.

 

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  • Aba MA, Quiroga MA, Auza N, Forsberg M & Kinsdahl H 1999 Control of ovarian activity in llamas (Lama glama) with medroxyprogesterone acetate. Reproduction in Domestic Animals 34 471476. (https://doi.org/10.1111/j.1439-0531.1999.tb01406.x)

    • Search Google Scholar
    • Export Citation
  • Adams GP, Matteri RL & Ginther OJ 1992 Effect of progesterone on ovarian follicles, emergence of follicular waves and circulating FSH in heifers. Journal of Reproduction and Fertility 96 627640. (https://doi.org/10.1530/jrf.0.0960627)

    • Search Google Scholar
    • Export Citation
  • Adams GP, Ratto MH, Huanca W & Singh J 2005 Ovulation-inducing factor in the seminal plasma of alpacas and llamas. Biology of Reproduction 73 452457. (https://doi.org/10.1095/biolreprod.105.040097)

    • Search Google Scholar
    • Export Citation
  • Adams GP, Ratto MH, Silva ME & Carrasco RA 2016 Ovulation-inducing factor (OIF/NGF) in seminal plasma: a review and update. Reproduction in Domestic Animals 51 (Supplement 2) 417. (https://doi.org/10.1111/rda.12795)

    • Search Google Scholar
    • Export Citation
  • Adams GP, Sumar J & Ginther OJ 1990 Effects of lactational and reproductive status on ovarian follicular waves in llamas (Lama glama). Journal of Reproduction and Fertility 90 535545. (https://doi.org/10.1530/jrf.0.0900535)

    • Search Google Scholar
    • Export Citation
  • Berland MA, Ulloa-Leal C, Barría M, Wright H, Dissen GA, Silva ME, Ojeda SR & Ratto MH 2016 Seminal plasma induces ovulation in llamas in the absence of a copulatory stimulus: role of nerve growth factor as an ovulation-inducing factor. Endocrinology 157 32243232. (https://doi.org/10.1210/en.2016-1310)

    • Search Google Scholar
    • Export Citation
  • Bogle OA, Ratto MH & Adams GP 2012 Ovulation-inducing factor (OIF) induces LH secretion from pituitary cells. Animal Reproduction Science 133 117122. (https://doi.org/10.1016/j.anireprosci.2012.06.006)

    • Search Google Scholar
    • Export Citation
  • Caba M, Pau KY, Beyer C, Gonzalez A, Silver R & Spies HG 2000 Coitus-induced activation of c-fos and gonadotropin-releasing hormone in hypothalamic neurons in female rabbits. Brain Research: Molecular Brain Research 78 6979. (https://doi.org/10.1016/s0169-328x(0000071-1)

    • Search Google Scholar
    • Export Citation
  • Caraty A, Lomet D, Sébert ME, Guillaume D, Beltramo M & Evans NP 2013 Gonadotrophin-releasing hormone release into the hypophyseal portal blood of the ewe mirrors both pulsatile and continuous intravenous infusion of kisspeptin: an insight into kisspeptin’s mechanism of action. Journal of Neuroendocrinology 25 537546. (https://doi.org/10.1111/jne.12030)

    • Search Google Scholar
    • Export Citation
  • Carrasco RA, Singh J & Adams GP 2018a Distribution and morphology of gonadotropin-releasing hormone neurons in the hypothalamus of an induced ovulator – the llama (Lama glama). General and Comparative Endocrinology 263 4350. (https://doi.org/10.1016/j.ygcen.2018.04.011)

    • Search Google Scholar
    • Export Citation
  • Carrasco RA, Singh J & Adams GP 2018b The relationship between gonadotropin releasing hormone and ovulation inducing factor/nerve growth factor receptors in the hypothalamus of the llama. Reproductive Biology and Endocrinology 16 83. (https://doi.org/10.1186/s12958-018-0402-6)

    • Search Google Scholar
    • Export Citation
  • Carrasco RA, Singh J, Ratto MH & Adams GP 2021 Neuroanatomical basis of the nerve growth factor ovulation-induction pathway in llamas. Biology of Reproduction 104 578588. (https://doi.org/10.1093/biolre/ioaa223)

    • Search Google Scholar
    • Export Citation
  • Carroll RS, Erskine MS, Doherty PC, Lundell LA & Baum MJ 1985 Coital stimuli controlling luteinizing hormone secretion and ovulation in the female ferret. Biology of Reproduction 32 925933. (https://doi.org/10.1095/biolreprod32.4.925)

    • Search Google Scholar
    • Export Citation
  • Clarke IJ & Cummins JT 1984 Direct pituitary effects of estrogen and progesterone on gonadotropin secretion in the ovariectomized ewe. Neuroendocrinology 39 267274. (https://doi.org/10.1159/000123990)

    • Search Google Scholar
    • Export Citation
  • d’Anglemont de Tassigny X, Ackroyd KJ, Chatzidaki EE & Colledge WH 2010 Kisspeptin signaling is required for peripheral but not central stimulation of gonadotropin-releasing hormone neurons by NMDA. Journal of Neuroscience 30 85818590. (https://doi.org/10.1523/JNEUROSCI.5486-09.2010)

    • Search Google Scholar
    • Export Citation
  • Ezzat A, Pereira A & Clarke IJ 2015 Kisspeptin is a component of the pulse generator for GnRH secretion in female sheep but not the pulse generator. Endocrinology 156 18281837. (https://doi.org/10.1210/en.2014-1756)

    • Search Google Scholar
    • Export Citation
  • Goodman RL & Karsch FJ 1980 Pulsatile secretion of luteinizing hormone: differential suppression by ovarian steroids. Endocrinology 107 12861290. (https://doi.org/10.1210/endo-107-5-1286)

    • Search Google Scholar
    • Export Citation
  • Hoffman GE, Murphy KJ & Sita LV 2016 The importance of titrating antibodies for immunocytochemical methods. Current Protocols in Neuroscience 76 2.12.12.12.37. (https://doi.org/10.1002/cpns.1)

    • Search Google Scholar
    • Export Citation
  • Hoffman GE, Smith MS & Verbalis JG 1993 C-fos and related immediate early gene products as markers of activity in neuroendocrine systems. Frontiers in Neuroendocrinology 14 173213. (https://doi.org/10.1006/frne.1993.1006)

    • Search Google Scholar
    • Export Citation
  • Huang EJ & Reichardt LF 2001 Neurotrophins: roles in neuronal development and function. Annual Review of Neuroscience 24 677736. (https://doi.org/10.1146/annurev.neuro.24.1.677)

    • Search Google Scholar
    • Export Citation
  • Imakawa K, Day ML, Zalesky DD, Garcia-Winder M, Kittok RJ & Kinder JE 1986 Regulation of pulsatile LH secretion by ovarian steroids in the heifer. Journal of Animal Science 63 162168. (https://doi.org/10.2527/jas1986.631162x)

    • Search Google Scholar
    • Export Citation
  • Iremonger KJ, Porteous R & Herbison AE 2017 Spike and neuropeptide-dependent mechanisms control GnRH neuron nerve terminal Ca2+ over diverse time scales. Journal of Neuroscience 37 33423351. (https://doi.org/10.1523/JNEUROSCI.2925-16.2017)

    • Search Google Scholar
    • Export Citation
  • Irwig MS, Fraley GS, Smith JT, Acohido BV, Popa SM, Cunningham MJ, Gottsch ML, Clifton DK & Steiner RA 2004 Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat. Neuroendocrinology 80 264272. (https://doi.org/10.1159/000083140)

    • Search Google Scholar
    • Export Citation
  • Karsch FJ, Cummins JT, Thomas GB & Clarke IJ 1987 Steroid feedback inhibition of pulsatile secretion of gonadotropin-releasing hormone in the ewe. Biology of Reproduction 36 12071218. (https://doi.org/10.1095/biolreprod36.5.1207)

    • Search Google Scholar
    • Export Citation
  • Kesner JS, Padmanabhan V & Convey EM 1982 Estradiol induces and progesterone inhibits the preovulatory surges of luteinizing hormone and follicle-stimulating hormone in heifers. Biology of Reproduction 26 571578. (https://doi.org/10.1095/biolreprod26.4.571)

    • Search Google Scholar
    • Export Citation
  • Lambert GM, Rubin BS & Baum MJ 1992 Sex difference in the effect of mating on c-fos expression in luteinizing hormone-releasing hormone neurons of the ferret forebrain. Endocrinology 131 14731480. (https://doi.org/10.1210/endo.131.3.1505478)

    • Search Google Scholar
    • Export Citation
  • Lee WS, Smith MS & Hoffman GE 1990 Luteinizing hormone-releasing hormone neurons express Fos protein during proestrus surge of luteinizing hormone. PNAS 87 51635167. (https://doi.org/10.1073/pnas.87.13.5163)

    • Search Google Scholar
    • Export Citation
  • Lee WW, Attardi B, Berghorn KA, Blaustein J & Hoffman GE 1997 Progesterone blockade of a luteinizing hormone surge blocks luteinizing hormone-releasing hormone Fos activation of its preoptic area afferents. Brain Research 778 272280. (https://doi.org/10.1016/S0006-8993(9700971-2)

    • Search Google Scholar
    • Export Citation
  • Milbrandt J 1986 Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells. PNAS 83 47894793. (https://doi.org/10.1073/pnas.83.13.4789)

    • Search Google Scholar
    • Export Citation
  • Moenter SM, Karsch FJ & Lehman MN 1993 Fos expression during the estradiol-induced gonadotropin-releasing hormone (GnRH) surge of the ewe: induction in GnRH and other neurons. Endocrinology 133 896903. (https://doi.org/10.1210/endo.133.2.8344224)

    • Search Google Scholar
    • Export Citation
  • Ratto MH, Delbaere LT, Leduc YA, Pierson RA & Adams GP 2011 Biochemical isolation and purification of ovulation-inducing factor (OIF) in seminal plasma of llamas. Reproductive Biology and Endocrinology 9 24. (https://doi.org/10.1186/1477-7827-9-24)

    • Search Google Scholar
    • Export Citation
  • Ratto MH, Huanca W, Singh J & Adams GP 2005 Local versus systemic effect of ovulation-inducing factor in seminal plasma of alpacas. Reproductive Biology and Endocrinology 3 29. (https://doi.org/10.1186/1477-7827-3-29)

    • Search Google Scholar
    • Export Citation
  • Ratto MH, Leduc YA, Valderrama XP, van Straaten KE, Delbaere LT, Pierson RA & Adams GP 2012 The nerve of ovulation-inducing factor in semen. PNAS 109 1504215047. (https://doi.org/10.1073/pnas.1206273109)

    • Search Google Scholar
    • Export Citation
  • Ratto MH, Singh J, Huanca W & Adams GP 2003 Ovarian follicular wave synchronization and pregnancy rate after fixed-time natural mating in llamas. Theriogenology 60 16451656. (https://doi.org/10.1016/s0093-691x(0300176-6)

    • Search Google Scholar
    • Export Citation
  • Rawlings NC, Jeffcoate IA & Rieger DL 1984 The influence of estradiol-17beta and progesterone on peripheral serum concentrations of luteinizing hormone and follicle stimulating hormone in the ovariectomized ewe. Theriogenology 22 473488. (https://doi.org/10.1016/0093-691x(8490047-5)

    • Search Google Scholar
    • Export Citation
  • Robinson JE & Kendrick KM 1992 Inhibition of luteinizing hormone secretion in the ewe by progesterone: associated changes in the release of gamma-aminobutyric acid and noradrenaline in the preoptic area as measured by intracranial microdialysis. Journal of Neuroendocrinology 4 231236. (https://doi.org/10.1111/j.1365-2826.1992.tb00164.x)

    • Search Google Scholar
    • Export Citation
  • Silva ME, Fernández A, Ulloa-Leal C, Adams GP, Berland MA & Ratto MH 2015 LH release and ovulatory response after intramuscular, intravenous, and intrauterine administration of β-nerve growth factor of seminal plasma origin in female llamas. Theriogenology 84 10961102. (https://doi.org/10.1016/j.theriogenology.2015.06.006)

    • Search Google Scholar
    • Export Citation
  • Silva ME, Smulders JP, Guerra M, Valderrama XP, Letelier C, Adams GP & Ratto MH 2011 Cetrorelix suppresses the preovulatory LH surge and ovulation induced by ovulation-inducing factor (OIF) present in llama seminal plasma. Reproductive Biology and Endocrinology 9 74. (https://doi.org/10.1186/1477-7827-9-74)

    • Search Google Scholar
    • Export Citation
  • Skinner DC, Evans NP, Delaleu B, Goodman RL, Bouchard P & Caraty A 1998 The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor. PNAS 95 1097810983. (https://doi.org/10.1073/pnas.95.18.10978)

    • Search Google Scholar
    • Export Citation
  • Tanco VM, Ratto MH, Lazzarotto M & Adams GP 2011 Dose-response of female llamas to ovulation-inducing factor from seminal plasma. Biology of Reproduction 85 452456. (https://doi.org/10.1095/biolreprod.111.091876)

    • Search Google Scholar
    • Export Citation
  • Veiga MF, Trasorras VL, Bianchi CP, Aba M, Moncalvo E, Chaves MG & Miragaya MH 2018 Administration of progesterone BioRelease LA inhibits follicular growth in llamas (Lama glama) regardless of follicle diameter at the start of the treatment. Reproduction in Domestic Animals 5313471352. (https://doi.org/10.1111/rda.13283)

    • Search Google Scholar
    • Export Citation
  • Wintermantel TM, Campbell RE, Porteus R, Bock D, Grone HJ, Todman MG, Korach KS, Greiner E, Perez CA & Schultz G et al. 2006 Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron 52 271280. (https://doi.org/10.1016/j.neuron.2006.07.023)

    • Search Google Scholar
    • Export Citation
  • Witkin JW, Xiao E, Popilskis S, Ferin M & Silverman AJ 1994 FOS expression in the gonadotropin-releasing hormone (GnRH) neuron does not increase during the ovarian steroid-induced GnRH surge in the rhesus monkey. Endocrinology 135 956961. (https://doi.org/10.1210/endo.135.3.8070392)

    • Search Google Scholar
    • Export Citation
  • Wu TJ, Segal AZ, Miller GM, Gibson MJ & Silverman AJ 1992 FOS expression in gonadotropin-releasing hormone neurons: enhancement by steroid treatment and mating. Endocrinology 131 20452050. (https://doi.org/10.1210/endo.131.5.1425409)

    • Search Google Scholar
    • Export Citation