Peripheral Administration of RF9 Does Not Affect Hypothalamic-PituitaryGonadal Axis in Normal Fed Adult Male Macaque
A B S T R A C T
Stress represses hypothalamic-pituitary-gonadal axis (HPG-axis) but RF9, a synthetic peptide, rescues such repression. To assess the role of RF9 in regulating HPG-axis under normal physiological conditions in higher primates, RF9 was administered to intact adult male rhesus monkeys and response of the HPG-axis was examined by measuring plasma testosterone as an end parameter of the axis. Control group (n=4) received normal saline whereas the treated group (n=4) received RF9. On the first day of experiment, four bolus injections of normal saline (1ml/animal) were administered intravenously at 2-hr interval to the control monkeys. Similarly, on the second day of experiment, treated group received four iv bolus injections of RF9 (0.1mg/kg BW) at 2-hr interval. Serial blood samples were collected at 20 min interval during a 6-hr period which started just after first saline/RF9 injection. Plasma testosterone levels were measured by using a specific EIA. Overall means of plasma testosterone levels and plasma testosterone area under curve (AUC) and overall mean testosterone and mean testosterone AUC in short time windows following each injection of RF9 and saline were comparable between the groups. Our results demonstrate that RF9 has no role in regulating HPG-axis under normal physiological conditions in adult male monkeys.
Keywords
RF9, normal fed monkeys, reproduction
Get access to the full version of this article.
Article Info
Article Type
Research ArticlePublication history
Received: Fri 19, Jun 2020Accepted: Mon 29, Jun 2020
Published: Fri 24, Jul 2020
Copyright
© 2023 Aalia Batool. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.DOI: 10.31487/j.CROGR.2020.02.03
Author Info
Madiha Wazir Rahim Ullah Aalia Batool Rabia Naz Muhammad Shahab
Corresponding Author
Aalia BatoolLaboratory of Reproductive Neuroendocrinology, Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
Figures & Tables
Get access to the full version of this article.
References
- R H Castillo, R L Matteri, D A Dumesic (1992) Luteinizing hormone synthesis in cultured fetal human pituitary cells exposed to gonadotropin-releasing hormone. J Clin Endocrinol Metab 75: 318-322. [Crossref]
- Rahim Ullah, Yan Su, Yi Shen, Chunlu Li, Xiaoqin Xu et al. (2017) Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: a novel model of obesity and puberty. Front Med 11: 266-276. [Crossref]
- T Hori, M Ide, T Miyake (1969) Pituitary regulation of preovulatory estrogen secretion in the rat. Endocrinol Jpn 16: 351-360. [Crossref]
- D J Bolt, H E Kelley, H W Hawk (1971) Release of LH by estradiol in cycling ewes. Biol Reprod 4: 35-40.
- A V Schally, A Arimura, A J Kastin, H Matsuo, Y Baba et al. (1971) Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science 173: 1036-1038. [Crossref]
- Themmen APN, I T Huhtaniemi (2000) Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 21: 551-583. [Crossref]
- F Wahab, M Shahab, R Behr (2015) The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction. J Endocrinol 225: R49-R66. [Crossref]
- Rahim Ullah, Yi Shen, Yu Dong Zhou, Ke Huang, Jun Fen Fu et al. (2016) Expression and actions of GnIH and its orthologs in vertebrates: Current status and advanced knowledge. Neuropeptides 59: 9-20. [Crossref]
- A Batool, R Naz, M Wazir, A Azam, R Ullah et al. (2014) Acute fasting-induced repression of the hypothalamic-pituitary-gonadal axis is reversed by RF-9 administration in the adult male macaque. Horm Metab Res 46: 927-832. [Crossref]
- R Pineda, D Garcia Galiano, M A Sanchez Garrido, M Romero, F Ruiz Pino et al. (2010) Characterization of the potent gonadotropin-releasing activity of RF9, a selective antagonist of RF-amide-related peptides and neuropeptide FF receptors: physiological and pharmacological implications. Endocrinology 151: 1902-1913. [Crossref]
- A Caraty, M Blomenröhr, G M T Vogel, D Lomet, C Briant et al. (2012) RF9 powerfully stimulates gonadotrophin secretion in the ewe: evidence for a seasonal threshold of sensitivity. J Neuroendocrinol 24: 725-736. [Crossref]
- Frédéric Simonin, Martine Schmitt, Jean Paul Laulin, Emilie Laboureyras, Jack H Jhamandas et al. (2006) RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia. Proc Natl Acad Sci U S A 103: 466-471. [Crossref]
- S Hinuma, Y Shintani, S Fukusumi, N Iijima, Y Matsumoto et al. (2000) New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals. Nat Cell Biol 2: 703-708. [Crossref]
- Takayoshi Ubuka, Hank Lai, Mari Kitani, Akane Suzuuchi, Viet Pham et al. (2009) Gonadotropin inhibitory hormone identification, cDNA cloning, and distribution in rhesus macaque brain. J Comp Neurol 517: 841-855. [Crossref]
- Lenka Maletínská, Anežka Tichá, Veronika Nagelová, Andrea Spolcová, Miroslava Blechová et al. (2013) Neuropeptide FF analog RF9 is not an antagonist of NPFF receptor and decreases food intake in mice after its central and peripheral administration. Brain Res 1498: 33-40. [Crossref]
- Le Min, Silvia Leon, Huan Li, Leonor Pinilla, Rona S Carroll et al. (2015) RF9 Acts as a KISS1R Agonist In Vivo and In Vitro. Endocrinology 156: 4639-4648. [Crossref]
- Xinhuai Liu, Allan E Herbison (2014) RF9 Excitation of GnRH Neurons Is Dependent Upon Kiss1r in the Adult Male and Female Mouse. Endocrinology 155: 4915-4924. [Crossref]
- Fazal Wahab, Farzana Aziz, Shahzad Irfan, Waheed Uz Zaman, Muhammad Shahab (2008) Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta). Life Sci 83: 633-637. [Crossref]
- F Wahab, R Bano, S Jabeen, S Irfan, M Shahab (2010) Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta). Horm Metab Res 42: 570-574. [Crossref]
- F Wahab, W uz Zaman, M Shahab (2012) Differential response of the primate HPG axis to N-methyl-D, L-aspartate, but not to Kisspeptin challenge under euglycemic and hypoglycemic conditions. Horm Metab Res 44: 451-457. [Crossref]
- R Pineda, D Garcia Galiano, M A Sanchez Garrido, M Romero, F Ruiz Pino et al. (2010) Characterization of the potent gonadotropin-releasing activity of RF9, a selective antagonist of RF-amide-related peptides and neuropeptide FF receptors: physiological and pharmacological implications. Endocrinology 151: 1902-1913. [Crossref]
- Rahim Ullah, Aalia Batool, Madiha Wazir, Rabia Naz, Tanzil Ur Rahman et al. (2017) Gonadotropin inhibitory hormone and RF9 stimulate hypothalamic-pituitary-adrenal axis in adult male rhesus monkeys. Neuropeptides 66: 1-7. [Crossref]
- J L Cameron (1996) Regulation of reproductive hormone secretion in primates by short-term changes in nutrition. Rev Reprod 1: 117-126. [Crossref]
- T Ordög, M D Chen, K T O'Byrne, J R Goldsmith, M A Connaughton et al. (1998) On the mechanism of lactational anovulation in the rhesus monkey. Am J Physiol 274: E665-E676. [Crossref]
- Tony M Plant, Mandi L Barker Gibb (2004) Neurobiological mechanisms of puberty in higher primates. Hum Reprod Update 10: 67-77. [Crossref]