Silla AJ , Calatayud NE , Trudeau VL .

             corticosteroid receptor signaling pathway

	Figure 1 Proposed simplified model for the neuroendocrine control of spawning in amphibians. The principal stimulatory neuropeptide gonadotropin-releasing hormone (GnRH) is released from hypothalamic nerve terminals in the median eminence and transported to the anterior pituitary, where it acts on G-protein coupled GnRH receptors on gonadotrophs to synthesize the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The effects of GnRH are modulated by numerous neurohormones with emerging functions (Vu and Trudeau, 2016). The inhibitory catecholamine dopamine (DA), which may reduce GnRH action and LH release, is shown. Once secreted, circulating LH and FSH act on their respective G-protein coupled receptors in the ovaries or testes to drive steroidogenesis and gamete release. Here, progesterone (P4) is converted through multiple enzymatic steps to testosterone (T), which is aromatized to estradiol (E2). Estradiol plays an additional role in stimulating the hepatic synthesis of the egg yolk vitellogenin in females (not shown). Sex steroids are involved in gonadal development, reproductive behaviours and both positive and negative feedback control of the hypothalamo–pituitary axis. Also shown are key aspects of the stress axis. The neuropeptide corticotropin-releasing factor (CRF) is released from hypothalamic nerve terminals in the median eminence and transported to the pituitary, where it acts on G-protein coupled CRF receptors on corticotrophs to drive the synthesis and processing of the pre-pro-opiomelaocortin precursor protein to generate the peptide adrenocorticotropic hormone (ACTH). The ACTH is released into the circulation and binds to melanocortin receptors on steroidogenic cells in the interrenal to stimulate corticosterone (CORT) synthesis, which in turn regulates metabolism and immune function and critically exerts negative feedback control on CRF and ACTH cells. Accumulating evidence indicates that CORT can negatively modulate reproductive processes at multiple sites (see * in Figure 1) along the hypothalamo–pituitary–gonadal (HPG) axis, including GnRH and DA neurons, gonadotrophs and gonads. Moreover, hypothalamic CRF neurons may project to GnRH neurons where they could inhibit GnRH release in several vertebrates, but this remains to be determined in amphibians. The neuropeptide arginine vasotocin (AVT) is produced in preoptic magnocellular neurons, can be released to the blood from the posterior pituitary and has critical roles in stimulating reproductive behaviours. The AVT system is a target of steroid action to modulate sexual behaviour. Although not well understood, the pineal hormone melatonin (MEL) is released in a time- and season-dependent manner at night and has a role to play in regulating reproductive cycles. Sex pheromones are not well described in anurans, but in urodeles, at least some are peptides. Arrowheads indicate stimulation, circles indicate inhibition and diamond heads indicate modulatory effects (stimulatory and inhibitory).
	Figure 2 (a) Mountain yellow-legged frog, R. muscosa (photo credit: Tali Hammond); (b) administration of hormones by intraperitoneal injection to an adult female (image taken from Calatayud et al., 2019 with permission from the Journal of Visual Experimentation).
	Figure 3 (a) Male northern corroboree frog, P. pengilleyi; (b) topical application of reproductive hormones by syringe application of drops on the ventral surface of P. pengilleyi. The topical application of a GnRH-a in 2017 generated in excess of 300 viable embryos from 18 clutches. Incorporating reproductive technologies into the existing captive breeding and reintroduction program for the northern corroboree frog will allow better control over the genetic management of the species, including the selective breeding of particular genotypes. Photo credits: Aimee Silla.

Ball, Hypothalamic control of the pars distalis in fishes, amphibians, and reptiles. 1981, Pubmed

Ball, Hypothalamic control of the pars distalis in fishes, amphibians, and reptiles. 1981, Pubmed
Borah, Seasonality in terai tree frog (Polypedates teraiensis): Role of light and temperature in regulation of seasonal breeding. 2019, Pubmed
Browne, Progesterone improves the number and quality of hormone induced Fowler toad (Bufo fowleri) oocytes. 2006, Pubmed
Browne, Sperm collection and storage for the sustainable management of amphibian biodiversity. 2019, Pubmed
Byrne, Evolutionary causes and consequences of sequential polyandry in anuran amphibians. 2012, Pubmed
Byrne, Genetic benefits of extreme sequential polyandry in a terrestrial-breeding frog. 2019, Pubmed
Calatayud, A hormone priming regimen and hibernation affect oviposition in the boreal toad (Anaxyrus boreas boreas). 2015, Pubmed
Calatayud, Ovarian control and monitoring in amphibians. 2018, Pubmed
Calatayud, Reproductive Techniques for Ovarian Monitoring and Control in Amphibians. 2019, Pubmed , Xenbase
Chabbi, Evidence for the involvement of dopamine in stress-induced suppression of reproduction in the cichlid fish Oreochromis mossambicus. 2015, Pubmed
Chand, Stress and reproduction: controversies and challenges. 2011, Pubmed
Clulow, Amphibian declines in the twenty-first century: why we need assisted reproductive technologies. 2014, Pubmed
Clulow, Differential success in obtaining gametes between male and female Australian temperate frogs by hormonal induction: A review. 2018, Pubmed
Clulow, Amphibian Assisted Reproductive Technologies: Moving from Technology to Application. 2019, Pubmed
Cockrem, Individual variation in glucocorticoid stress responses in animals. 2013, Pubmed
Coddington, Effect of acute captivity stress on plasma concentrations of corticosterone and sex steroids in female whistling frogs, Litoria ewingi. 1995, Pubmed
Creighton, Influence of dopamine D2-type receptors on motor behaviors in the green tree frog, Hyla cinerea. 2014, Pubmed
Czuchlej, Effect of glucocorticoids on androgen biosynthesis in the testes of the toad Rhinella arenarum (Amphibia, Anura). 2019, Pubmed
Davis, Corticosterone suppresses vasotocin-enhanced clasping behavior in male rough-skinned newts by novel mechanisms interfering with V1a receptor availability and receptor-mediated endocytosis. 2015, Pubmed
de Assis, Vocal and territorial behavior in the Smith frog (Hypsiboas faber): relationships with plasma levels of corticosterone and testosterone. 2012, Pubmed
Della Togna, Effects of hormonal stimulation on the concentration and quality of excreted spermatozoa in the critically endangered Panamanian golden frog (Atelopus zeteki). 2017, Pubmed
Della Togna, Evaluating amphibian biobanking and reproduction for captive breeding programs according to the Amphibian Conservation Action Plan objectives. 2020, Pubmed , Xenbase
Denari, 11beta-hydroxysteroid dehydrogenase in the testis of Bufo arenarum: changes in its seasonal activity. 2005, Pubmed
Di Fiore, Celebrating 50+ years of research on the reproductive biology and endocrinology of the green frog: An overview. 2020, Pubmed
Dufour, Dopaminergic inhibition of reproduction in teleost fishes: ecophysiological and evolutionary implications. 2005, Pubmed
Dufour, Neuroendocrine control by dopamine of teleost reproduction. 2010, Pubmed
Dugas, Carotenoid supplementation enhances reproductive success in captive strawberry poison frogs (Oophaga pumilio). 2013, Pubmed
Dziminski, Patterns and fitness consequences of intraclutch variation in egg provisioning in tropical Australian frogs. 2005, Pubmed
Eisthen, Ambiguities in the relationship between gonadal steroids and reproduction in axolotls (Ambystoma mexicanum). 2012, Pubmed
Ferrie, Nutrition and health in amphibian husbandry. 2014, Pubmed , Xenbase
Fitzgerald, Ovarian dysgerminomas in two mountain chicken frogs (Leptodactylus fallax). 2007, Pubmed
Gracia-Navarro, Subcellular localization of gonadotrophic hormones LH and FSH in frog adenohypophysis using double-staining immunocytochemistry. 1987, Pubmed
Graham, Ultrasound imaging improves hormone therapy strategies for induction of ovulation and in vitro fertilization in the endangered dusky gopher frog (Lithobates sevosa). 2018, Pubmed
Green, Ovarian hyperstimulation syndrome in gonadotropin-treated laboratory South African clawed frogs (Xenopus laevis). 2007, Pubmed , Xenbase
Guy, Sperm collection and cryopreservation for threatened newt species. 2020, Pubmed
Guy, Evaluation of different temporal periods between hormone-induced ovulation attempts in the female Fowler's toad Anaxyrus fowleri. 2020, Pubmed
Holz, Mortality in northern corroboree frog tadpoles (Pseudophryne pengilleyi) associated with Tetrahymena-like infection. 2015, Pubmed
Houck, Courtship behavior and plasma levels of androgens and corticosterone in male marbled salamanders, Ambystoma opacum (ambystomatidae). 1996, Pubmed
Hunter, Presence of the amphibian chytrid fungus Batrachochytrium dendrobatidis in threatened corroboree frog populations in the Australian Alps. 2010, Pubmed
Joshi, Interrelationship among annual cycles of sex steroids, corticosterone and body condition in Nyctibatrachus humayuni. 2018, Pubmed
Kaiser, Reproductive and immune effects of chronic corticosterone treatment in male White's treefrogs, Litoria caerulea. 2015, Pubmed
Keogh, The effect of gentamicin on sperm motility and bacterial abundance during chilled sperm storage in the Booroolong frog. 2017, Pubmed
Keogh, Effect of long-term dietary beta-carotene supplementation on sperm concentration and motility in an endangered amphibian. 2018, Pubmed
Keogh, Dose and life stage-dependent effects of dietary beta-carotene supplementation on the growth and development of the Booroolong frog. 2018, Pubmed
Kouba, A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus). 2012, Pubmed
Kouba, Artificial fertilization for amphibian conservation: current knowledge and future considerations. 2009, Pubmed
Kouba, Applied reproductive technologies and genetic resource banking for amphibian conservation. 2009, Pubmed
Kubokawa, Follicle-stimulating hormone (FSH) receptors in the testis of the newt, Cynops pyrrhogaster, and comparison of temperature dependency of the receptors with those of the other vertebrates. 1980, Pubmed , Xenbase
Kubokawa, Receptors for native gonadotropins in amphibian liver. 1987, Pubmed
Lee, Untargeted Metabolomics and Steroid Signatures in Urine of Male Pattern Baldness Patients after Finasteride Treatment for a Year. 2020, Pubmed
Lehman, Environmental influence on ovulation and embryonic development in Rana pipiens. 1977, Pubmed
Licht, Seasonal and stress related changes in plasma gonadotropins, sex steroids, and corticosterone in the bullfrog, Rana catesbeiana. 1983, Pubmed
Licht, Reproductive endocrinology of reptiles and amphibians: gonadotropins. 1979, Pubmed
Licht, The nature and distribution of gonadotropin-releasing hormones in brains and plasma of ranid frogs. 1994, Pubmed
Madelaire, Breeding under unpredictable conditions: Annual variation in gonadal maturation, energetic reserves and plasma levels of androgens and corticosterone in anurans from the Brazilian semi-arid. 2016, Pubmed
Mansour, Collection of gametes from live axolotl, Ambystoma mexicanum, and standardization of in vitro fertilization. 2011, Pubmed
McDonough, Frequency of exogenous hormone therapy impacts spermiation in male Fowler's toad (Bufo fowleri). 2016, Pubmed
Mendonça, Changes in hormone levels in relation to breeding behavior in male bullfrogs (Rana catesbeiana) at the individual and population levels. 1985, Pubmed
Michael, Induced ovulation and egg deposition in the direct developing anuran Eleutherodactylus coqui. 2004, Pubmed
Millar, Gonadotropin-releasing hormone receptors. 2004, Pubmed
Minteer, Ecological ethics in captivity: balancing values and responsibilities in zoo and aquarium research under rapid global change. 2013, Pubmed
Miyazaki, A novel method for induction of pairing in Xenopus by addition of steroids into the water. 2013, Pubmed , Xenbase
Moore, Stress-induced inhibition of reproduction: evidence of suppressed secretion of LH-RH in an amphibian. 1985, Pubmed
Moore, Stress, reproduction, and adrenocortical modulation in amphibians and reptiles. 2003, Pubmed
Moore, Stress-induced inhibition of sexual behavior: corticosterone inhibits courtship behaviors of a male amphibian (Taricha granulosa). 1984, Pubmed
Nagel, Non-invasive methods to measure inter-renal function in aquatic salamanders-correlating fecal corticosterone to the environmental and physiologic conditions of captive Necturus. 2019, Pubmed
Narayan, Inverse urinary corticosterone and testosterone metabolite responses to different durations of restraint in the cane toad (Rhinella marina). 2012, Pubmed
Narayan, Individual variation and repeatability in urinary corticosterone metabolite responses to capture in the cane toad (Rhinella marina). 2012, Pubmed
Ogawa, Induction of ovulation in Xenopus without hCG injection: the effect of adding steroids into the aquatic environment. 2011, Pubmed , Xenbase
Oh, Differential G protein coupling preference of mammalian and nonmammalian gonadotropin-releasing hormone receptors. 2003, Pubmed
Orchinik, Plasma steroid concentrations change in response to sexual behavior in Bufo marinus. 1988, Pubmed
O'Rourke, Nontraditional Laboratory Animal Species (Cephalopods, Fish, Amphibians, Reptiles, and Birds). 2018, Pubmed
Polzonetti-Magni, Gonadotropins and reproductive function in the anuran amphibian, Rana esculenta. 1998, Pubmed
Poo, Sperm output and body condition are maintained independently of hibernation in an endangered temperate amphibian. 2019, Pubmed
Popesku, The goldfish (Carassius auratus) as a model for neuroendocrine signaling. 2008, Pubmed
Romero, The Reactive Scope Model - a new model integrating homeostasis, allostasis, and stress. 2009, Pubmed
Romero, Seasonal changes in plasma glucocorticoid concentrations in free-living vertebrates. 2002, Pubmed
Roth, Effects of age, weight, hormones, and hibernation on breeding success in boreal toads (Bufo boreas boreas). 2010, Pubmed
Rowson, Non-invasive treatments of luteinizing hormone-releasing hormone for inducing spermiation in American (Bufo americanus) and Gulf Coast (Bufo valliceps) toads. 2001, Pubmed
Silla, Hormone-induced sperm-release in the critically endangered Booroolong frog (Litoria booroolongensis): effects of gonadotropin-releasing hormone and human chorionic gonadotropin. 2019, Pubmed
Silla, Effects of luteinizing hormone-releasing hormone and arginine-vasotocin on the sperm-release response of Günther's Toadlet, Pseudophryne guentheri. 2010, Pubmed
Silla, Effect of priming injections of luteinizing hormone-releasing hormone on spermiation and ovulation in Gϋnther's toadlet, Pseudophryne guentheri. 2011, Pubmed
Silla, Artificial fertilisation in a terrestrial toadlet (Pseudophryne guentheri): effect of medium osmolality, sperm concentration and gamete storage. 2013, Pubmed
Silla, The Role of Reproductive Technologies in Amphibian Conservation Breeding Programs. 2019, Pubmed , Xenbase
Silla, Hormone-induced ovulation and artificial fertilisation in four terrestrial-breeding anurans. 2021, Pubmed
Silla, The effect of injection and topical application of hCG and GnRH agonist to induce sperm-release in the roseate frog, Geocrinia rosea. 2020, Pubmed
Silla, Hormone-induced spawning of the critically endangered northern corroboree frog Pseudophryne pengilleyi. 2018, Pubmed
Silla, Investigating patterns in the spermiation response of eight Australian frogs administered human chorionic gonadotropin (hCG) and luteinizing hormone-releasing hormone (LHRHa). 2012, Pubmed
Smalley, Vitellogenic cycles in laboratory-maintained females of the leopard frog, Rana pipiens. 1983, Pubmed
Son, Development and validation of an LC-MS/MS method for profiling 39 urinary steroids (estrogens, androgens, corticoids, and progestins). 2020, Pubmed
Sotowska-Brochocka, Dopaminergic inhibition of gonadotropic release in hibernating frogs, Rana temporaria. 1994, Pubmed
Sotowska-Brochocka, The stimulatory and inhibitory role of the hypothalamus in the regulation of ovulation in grass frog, Rana temporaria L. 1988, Pubmed
Sotowska-Brochocka, Effect of infundibular lesions on GnRH and LH release in the frog, Rana temporaria, during hibernation. 1992, Pubmed
Teitsma, Identification of potential sites of cortisol actions on the reproductive axis in rainbow trout. 1998, Pubmed
Trudeau, Efficient induction of spawning of northern leopard frogs (Lithobates pipiens) during and outside the natural breeding season. 2013, Pubmed
Trudeau, Multimodal hypothalamo-hypophysial communication in the vertebrates. 2020, Pubmed
Trudeau, Hormonal induction of spawning in 4 species of frogs by coinjection with a gonadotropin-releasing hormone agonist and a dopamine antagonist. 2010, Pubmed
Turner, Administration of substances to laboratory animals: routes of administration and factors to consider. 2011, Pubmed
Vu, Time- and dose-related effects of a gonadotropin-releasing hormone agonist and dopamine antagonist on reproduction in the Northern leopard frog (Lithobates pipiens). 2017, Pubmed
Vu, Neuroendocrine control of spawning in amphibians and its practical applications. 2016, Pubmed
Wang, Three distinct types of GnRH receptor characterized in the bullfrog. 2001, Pubmed , Xenbase
Woodley, An acute stressor alters steroid hormone levels and activity but not sexual behavior in male and female Ocoee salamanders (Desmognathus ocoee). 2010, Pubmed
Yamanouchi, Positive cooperative action of follicle-stimulating hormone on binding of luteinizing hormone to testicular receptors from the bullfrog (Rana catesbeiana). 1990, Pubmed
Yao, Distribution and corticosteroid regulation of glucocorticoid receptor in the brain of Xenopus laevis. 2008, Pubmed , Xenbase