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Arginine vasotocin (AVT) and isotocin (IT) in fish brain: diurnal and seasonal variations.

An HPLC assay with solid-phase extraction and fluorescence derivatization was developed for measurement of arginine vasotocin (AVT) and isotocin (IT) in the neural tissues of fish. The efficiency and usefulness of the method have been verified in experiments by examination of peptides concentrations in brains of three fish species. The day-night changes in neuropeptides levels have been studied in brains of adult sea bream (Sparus aurata) and juvenile Atlantic salmon (Salmo salar). Seasonal fluctuations have been investigated in brains of three-spined sticklebacks (Gasterosteus aculeatus). The AVT and IT biosynthesis in brain seems to be controlled independently and probably each neuropeptide plays a different role in a circadian time-keeping system and an endocrine calendar in fish.

Animals↗

Determination of the neuropeptides arginine vasotocin and isotocin in brains of three-spined sticklebacks (Gasterosteus aculeatus) by off-line solid phase extraction-liquid chromatography-electrospray tandem mass spectrometry.

A method based on solid phase extraction (SPE) followed by liquid chromatography-electrospray ionisation tandem mass spectrometry for the determination of the nonapeptides arginine vasotocin (AVT) and isotocin (IT) in brains of three-spined sticklebacks (Gasterosteus aculeatus) is described. Separation and detection were optimized using synthetic standards. Limits of detection (LOD) for standard solutions were 160 pg mL(-1) for AVT and 250 pg mL(-1) for IT. The SPE procedure hardly affected the LODs for standard solutions. Mainly because of ion suppression, LODs for AVT and IT in brains were approximately 5 and 25 pg mg(-1), respectively. The concentrations determined in the brain of several fishes ranged from 10 to 500 pg mg(-1) for AVT and from 400 to 4000 pg mg(-1) for IT.

Animals↗

Early embryonic administration of xenoestrogens alters vasotocin system and male sexual behavior of the Japanese quail.

The copulatory behavior and the parvocellular vasotocin (VT) system of the nucleus of the stria terminalis (BST) are sexually dimorphic in the Japanese quail. Embryonic administration of estradiol benzoate (EB) induces an organizational effect determining the disappearance of such a dimorphism (male shows behavior and cerebral phenotype of the female). The VT parvocellular system can therefore be considered an accurate marker of the sexual differentiation of brain circuits and a very sensitive indicator of the activity of estrogen-like substances on neural circuits. To test this hypothesis we administered diethylstilbestrol (DES), a powerful synthetic xenoestrogen, genistein (GEN), a phytoestrogen produced by soy, and bisphenol A (BPA). After 3 days of incubation, quail eggs were injected with vehicle, EB, DES, GEN or BPA. Administration of BPA caused an early blockage of development and no further analyses were done on the BPA groups. At puberty, the copulatory behavior of EB- or DES-treated male quail was totally abolished, whereas only the highest doses of GEN determined a significant decrease of the behavior. After the tests, the animals were sacrificed and perfused. The fractional area (FA) covered by VT immunoreactivity was analyzed in BST, medial preoptic nucleus, and lateral septum by computerized image analysis. The FA was significantly reduced after treatment with EB, DES and GEN at high doses. These results confirm that the sexually dimorphic VT system of the Japanese quail is a sensible indicator of the effects of xenoestrogens at the level of the central nervous system.

Animals↗

Determination of arginine-vasotocin and isotocin in fish plasma with solid-phase extraction and fluorescence derivatization followed by high-performance liquid chromatography.

A new HPLC assay for plasma arginine-vasotocin (AVT) and isotocin (IT) determination based on fluorescence detection preceded by combination of solid-phase extraction (SPE) and fluorescence derivatization is presented. Plasma samples retained on solid support were purified and then derivatized by the fluorescent compound 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). The peptide derivatives were eluted from cartridges, pre-concentrated and analyzed by HPLC system with fluorescent detection. The separation was carried out on a reversed-phase column with solvent gradient system. The assay was linear in the range 15-220 pmol ml(-1) for AVT r2=0.998 and 10-220 pmol ml(-1) for IT r2=0.996. The detection limits for AVT and IT were 0.8 and 0.5 pmol ml(-1) (3:1, signal-to-noise), respectively. The recoveries of derivatized hormones were in the range 89-93%. Both of the inter- and intra-day assay precision were below 5.5 and 9% for AVT and IT, respectively. The assay should be also applicable to plasma and tissue samples from other animals with only minor modification.

Animals↗

Gonadotropin-releasing hormones modulate electrical activity of vasotocin and isotocin neurons in the brain of rainbow trout.

Gonadotropin-releasing hormone (GnRH) is widely distributed in the vertebrate brains; however, its significance in the brain function is poorly understood. Both GnRH and vasopressin-family hormones are involved in control of reproductive behavior. Anatomical evidence indicated the possible action of GnRH on classical neurosecretory neurons. In the present study, we examined whether GnRH modulates electrical activity of vasotocin (VT) and isotocin (IT) neurons in the brain of rainbow trout (Oncorhynchus mykiss). Two forms of GnRH, salmon GnRH and chicken GnRH II, are present in the rainbow trout brain, and their fibers are localized in the close vicinity of VT and IT neurons. Applications of both GnRH forms elevated the frequency of cell-type-specific synchronous Ca(2+) pulses in VT and IT neurons that are blocked by a GnRH-receptor antagonist. Our results showed facilitatory actions of GnRHs on VT and IT neurons, suggesting that GnRH neurons modulate classical neurosecretory neurons to control reproductive behavior.

Action Potentials↗

Comparison of brain arginine-vasotocin and corticotrophin-releasing factor for physiological responses in chicks.

Arginine-vasotocin (AVT), a non-mammalian homologue of mammalian arginine-vasopressin, is a stress-related peptide in the brain of birds. The aim of the present study was to determine the effects of intracerebroventricular (ICV) injection of AVT on feeding behavior, body temperature, corticosterone release and several behavioral parameters in chicks. These effects were compared with those of corticotrophin-releasing factor (CRF), another stress-related peptide. The ICV injection of AVT inhibited feeding behavior, increased rectal temperature, and increased plasma corticosterone concentrations, but these effects were weaker than those of CRF. AVT induced hypoactivity as evidenced by decreased vocalization and stepping while CRF induced hyperactivity. The present results demonstrate that some functions of brain AVT are similar to those of CRF, although these effects are weaker than those induced by CRF. However, some AVT-induced behaviors were different from CRF, indicating that the physiological roles of AVT in the regulation of stress behavior are different from those of CRF in chicks.

Animals↗

Functional organization of preoptic vasotocin and isotocin neurons in the brain of rainbow trout: central and neurohypophysial projections of single neurons.

Preoptic magnocellular neurosecretory cells (NSCs) in the brain of rainbow trout show synchronization of periodic Ca(2+) pulses, patterns of which differ between vasotocin (VT) and isotocin (IT) neurons. To provide neuroanatomical bases of the synchronized periodic Ca(2+) pulses and their biological implications, we examined the organization of preoptic VT and IT neurons in the brain of rainbow trout. The cytoarchitecture of the preoptic neurosecretory system was characterized by a confocal double-color immunofluorescence. Two to five VT neurons, and also IT neurons, aggregate to form cell-type specific clusters. VT clusters tend to localize medially, while IT clusters laterally. VT neurons are closely apposed at the proximal neuronal processes. A Golgi-like immunohistochemistry demonstrated that VT and IT fibers distribute widely in the brain, such as ventral telencephalon, diencephalon, and various mesencephalic structures, in addition to the neurohypophysial projections. Projections from single VT and IT neurons were examined by an intracellular staining with biocytin injection in a sagittally hemisected brain preparation, which contains the entire forebrain region. Single VT and IT neurons project toward the pituitary and the extrahypothalamic regions. Some IT neurons, but not VT neurons, were dye-coupled. These results support the idea that the same types of NSCs are connected to form cell-type-specific networks responsible for the synchronization of periodic Ca(2+) pulses. The organization of the preoptic neurosecretory system shown in the present study is suitable for the simultaneous control of neurohypophysial and extrahypothalamic outputs through the synchronization of electrical activity.

Animals↗

Losartan blocks drinking and cFos expression induced by central ornithine vasotocin in rats.

We previously reported that an intracerebroventricular (icv) injection of the oxytocin receptor antagonist ornithine vasotocin (OVT) caused water and saline intakes, a pressor response, and Fos-like immunoreactivity (Fos-IR) in the median preoptic nucleus of the rat brain. In the present report, rats receiving an icv injection of isotonic saline vehicle followed by an icv injection of 10 microg of OVT 20 min later drank 5.5+/-1.1 ml of total water and saline intake in 60 min after the OVT; rats receiving 10 microg of losartan before the OVT drank only 0.9+/-0.3 ml of total fluid. In a separate study, rats were treated as above except that they were not allowed to drink and were perfused for analysis of Fos-IR in the median preoptic nucleus at 90 min. Fos-IR in the dorsal part of the median preoptic nucleus was significantly suppressed from 2.69+/-0.57 cells per 10,000 square mum in vehicle-treated rats to 0.89+/-0.20 in losartan-treated rats. Losartan alone had no effect on Fos-IR. Losartan did not reduce intake of saccharin in a dessert test. This suggests that the OVT-induced drinking may result from an activation or disinhibition of angiotensin type AT1 receptors in the median preoptic nucleus.

Angiotensin II Type 1 Receptor Blockers↗

Variation in vasotocin immunoreactivity in the brain of recently isolated populations of a death valley pupfish, Cyprinodon nevadensis.

Pupfishes in the Death Valley region of California and Nevada comprise a monophyletic group of populations that became isolated in remote streams and springs over the past 20,000 years. These aquatic habitats show considerable ecological diversity, and allopatric populations have evolved differences in morphology and behavior. Here we investigated whether the divergence of pupfish populations in Death Valley might be associated with changes in arginine vasotocin (AVT). We used immunocytochemistry to compare the expression of AVT in the brain of Amargosa pupfish (Cyprinodon nevadensis) from two Death Valley populations: (1) the Amargosa River-a highly variable desert stream containing the Cyprinodon nevadensis amargosae subspecies, and (2) Big Spring-a comparatively stable springhead and outflow inhabited by Cyprinodon nevadensis mionectes. These particular populations have been isolated from each other for only 400-4000 years. In both populations AVT-immunoreactive somata localized to parvocellular and magnocellular neurons in the preoptic area, with AVT-immunoreactive fibers extending ventrolaterally to innervate the pituitary. We found that both parvocellular and magnocellular AVT-immunoreactive neurons were significantly larger in males and females from the Amargosa River population than in same sex pupfish from Big Spring. Our findings suggest that the divergent ecological conditions of these two habitats have brought about changes in AVT pathways in the brain.

Animals↗

Plasma aldosterone, angiotensin II, and arginine vasotocin concentrations in the toad, Bufo marinus, following osmotic treatments.

To clarify the physiological roles of the renin-angiotensin-aldosterone system (RAAS) and arginine vasotocin (AVT) on body fluid regulation in amphibians, we measured plasma concentrations of aldosterone (ALDO), angiotensin II (ANG II), and AVT after various osmotic challenges in the marine toad, Bufo marinus (Bufonidae). Hematocrit value (Ht) as an indicator of plasma volume, plasma osmolality and concentrations of plasma components (Na(+), Cl(-), K(+), and urea) were also measured. The toads were maintained under various osmotic treatments for 7 days. In dehydrated toads, plasma concentrations of ALDO, ANG II, AVT, and all plasma components measured were increased. In toads maintained in 300 mosmol/kg H(2)O NaCl solution, plasma osmolality, Na(+), Cl(-), urea, and plasma AVT concentrations were significantly increased, and Ht and plasma concentrations of ALDO and ANG II were significantly decreased. In toads maintained in tap water, plasma osmolality, and concentrations of Na(+) and ALDO were significantly decreased. We also estimated total body water (TBW), plasma volume (PV) using Evans Blue dye and Ht in the toads under various osmotic treatments. In dehydrated toads, TBW and PV were significantly decreased and Ht was significantly increased in comparison with those of control. In toads maintained in 300 mosmol/kg H(2)O NaCl solution, TBW and PV were significantly increased and Ht was significantly decreased in comparison with those of control. There was a significant negative correlation between Ht and PV or TBW. These results show that dehydration, which induces hypovolemic and hyperosmotic conditions, stimulates increases of plasma ALDO, ANG II, and AVT concentrations, while hypervolemic treatment induces decreases of plasma ALDO and ANG II concentrations. There were significant correlations between plasma osmolality and AVT concentration, between Ht and concentrations of RAAS hormones, and between plasma concentrations of ALDO and ANG II. These results suggest that volumetric and osmometric systems regulated by RAAS hormones and AVT are present in B. marinus.

Adaptation, Physiological↗

Renal responses to mesotocin in Western painted turtles compared with the antidiuretic response to arginine vasotocin.

We have examined the renal responses to the two neurohypophysial peptides mesotocin (MT) and arginine vasotocin (AVT) in Western painted turtles (Chrysemis picta). Ureteral urine was collected, after removal of the urinary bladder, to exclude modification by trans-bladder fluxes of ions and or water. Test doses of MT ranged from 5 to 500 ng kg(-1) i.v. but only the uppermost pharmacological doses of 300 and 500 ng kg(-1) were followed by even a small reduction in GFR, a renal tubular antidiuresis, and a decrease in percent relative free-water one word clearance. A much lower, physiological, dose of 5 ng kg(-1) of AVT attenuated significantly the GFR for 30 min and decreased the percent relative free-water clearance until the end of a 150 min observation period. This is the first report of the renal response to MT in a reptile. It was concluded that MT is not a diuretic hormone, as it is in amphibians and that AVT may be the naturally occurring antidiuretic hormone in the Chelonians.

Animals↗

The effects of freshwater to seawater transfer on circulating levels of angiotensin II, C-type natriuretic peptide and arginine vasotocin in the euryhaline elasmobranch, Carcharhinus leucas.

This study examined the effect of transfer to increased environmental salinity on the circulating levels of angiotensin II (ANG II), C-type natriuretic peptide (CNP), and arginine vasotocin (AVT) in the euryhaline elasmobranch, Carcharhinus leucas. Plasma levels of ANG II and CNP were significantly increased in C. leucas chronically acclimated to seawater (SW) in comparison to freshwater (FW) acclimated fish. There was no difference in plasma AVT levels. Acute transfer of FW fish to 75% SW induced an increase in plasma ANG II levels within 12 h, and subsequent transfer from 75 to 100% SW further increased plasma ANG II levels at both 24 and 72 h. No change in plasma CNP was observed during acute transfer to increased salinity. However, a significant increase in plasma AVT levels was observed following 96 h in 75% SW and 24 h in 100% SW. In chronically SW acclimated C. leucas plasma osmolality, sodium, chloride, and urea were all significantly higher than FW acclimated fish but there was no difference in haematocrit. Acute transfer of C. leucas to 75% SW induced a significant increase in plasma osmolality, sodium and urea concentrations within 96 h of transfer. Subsequent transfer from 75 to 100% SW induced a further increase in these variables within 24 h in addition to a significant increase in plasma chloride above control levels. Haematocrit did not differ between the experimental and control groups throughout the acute study. Circulating levels of ANG II were significantly correlated to plasma, sodium, chloride, and urea concentrations during acclimation to SW. Conversely, circulating levels of CNP and AVT did not correlate to plasma osmolytes, however, CNP was significantly correlated to haematocrit during acclimation to seawater.

Acclimatization↗

Kidney function and the role of arginine vasotocin in three agamid lizards from habitats of differing aridity in Western Australia.

Western Australian agamid lizards are diverse and inhabit mesic to very arid areas of the state. Although reptilian kidneys are unable to elaborate hyperosmotic urine, we hypothesised that the renal system of lizards inhabiting arid areas would display an enhanced ability to conserve water under the control of the antidiuretic peptide hormone, arginine vasotocin (AVT). To examine this, the renal physiological and endocrine responses to osmotic challenge in three closely-related Australian agamid lizards inhabiting arid, semi-arid, and mesic environments were studied. The species studied were Pogona minor (mesic), Ctenophorus salinarum (semi-arid), and Ctenophorus nuchalis (arid). Circulating AVT was assayed and renal variables such as glomerular filtration rate (GFR), urine flow rate (V), and fractional reabsorption of filtrate FRH2O were measured in response to hypernatraemia, water load, and dehydration. Hypernatraemia and dehydration induced antidiuresis in all three species through similar mechanisms involving both glomerular and tubular responses. However, in salt-loaded P. minor the response was largely glomerular in nature, as FRH2O did not increase relative to the hydrated condition. The magnitude of the antidiuretic response was also greater in P. minor, indicating a greater sensitivity to osmotic challenge. Plasma concentrations of AVT were significantly correlated with FRH2O in P. minor (r2=0.38, P=0.025), but with GFR in C. nuchalis (r2=0.16, P=0.041). We found that the control and mechanisms of renal function among these lizards were largely similar, and there was little support for the hypothesis that arid lizards possess physiological adaptations not present in closely-related mesic lizards. Yet, differences remain in their response to hypernatraemia which may reflect the aridity of their different environments, or their varying habits.

Acclimatization↗

Arginine vasotocin a key hormone in fish physiology and behaviour: a review with insights from mammalian models.

The arginine vasotocin (AVT) neuroendocrine system clearly provides integrative regulation of many aspects of fish physiology and behaviour, including circadian and seasonal biology, responses to stress, metabolism, reproduction, cardiovascular function, and osmoregulation. These are all considered here providing an important context for the design of experiments and interpretation of results for investigations of specific aspects of AVT function. Salt and water balance is a consistent function from fish to mammals and is examined in more detail. Both AVT and AVP secretion is sensitive to hyperosmotic stimuli and associated cellular dehydration, while hypovolaemia would appear less important. AVT and AVP both mediate renal water conservation, though actions involve different receptors and precise targets in fish (V1) and mammals (V2). The actions of AVT to promote gill NaCl extrusion in fish are conserved in the AVP-induced natriuresis in mammalian kidney to support restoration of plasma osmolality. The AVT/AVP regulatory mechanisms involve both altered neurohypophysial peptide secretion and changes in target-tissue receptor expression/modulation of action. Both mechanisms importantly afford integration with the actions of other related hormone systems.

Animals↗

Osmoregulatory and metabolic changes in the gilthead sea bream Sparus auratus after arginine vasotocin (AVT) treatment.

The influence of arginine vasotocin (AVT) on osmoregulation and metabolism in gilthead sea bream Sparus auratus was evaluated by two experimental approaches. In the first, seawater (SW, 36 ppt)-acclimatized fish were injected intraperitoneally with vehicle (vegetable oil) or two doses of AVT (0.5 and 1 microg/g body weight). Twenty-four hours later, eight fish from each group were sampled; the remaining fish were transferred to low saline water (LSW, 6 ppt, hypoosmotic test), SW (transfer control), and hypersaline water (HSW, 55 ppt, hyperosmotic test). After another 24h (48-h post-injection), fish were sampled. The only significant effect observed was the increase of sodium levels in AVT-treated fish transferred to HSW. In the second experiment, fish were injected intraperitoneally with slow-release vegetable oil implants (mixture 1:1 of coconut oil and seeds oil) alone or containing AVT (1 microg/g body weight). After 3 days, eight fish from each group were sampled; the remaining fish were transferred to LSW, SW, and HSW as above, and sampled 3 days later (i.e. 6 days post-injection). In the AVT-treated group transferred from SW to SW, a significant increase vs. control was observed in gill Na(+),K(+)-ATPase activity. Kidney Na(+),K(+)-ATPase activity decreased in the AVT-treated group transferred to LSW and no changes were observed in the other groups. These osmoregulatory changes suggest a role for AVT during hyperosmotic acclimation based on changes displayed by gill Na(+),K(+)-ATPase activity. AVT treatment increased plasma cortisol levels in fish transferred to LSW and HSW. In addition, AVT treatment affected parameters of carbohydrate, lipid, amino acid, and lactate metabolism in plasma and tissues (gills, kidney, liver, and brain). The most relevant effects were the increased potential of liver for glycogen mobilization and glucose release resulting in increased plasma levels of glucose in AVT-treated fish transferred to LSW and HSW. These changes may be related to the energy repartitioning process occurring during osmotic adaptation of S. auratus to extreme environmental salinities and could be mediated by increased levels of cortisol in plasma.

Acclimatization↗

Effect of hypernatraemia and the neurohypophysial peptide, arginine vasotocin (AVT) on behavioural thermoregulation in the agamid lizard, Ctenophorus ornatus.

Hypernatraemia induced by chronic injections of sodium chloride provokes thermal depression in the agamid lizard, Ctenophorus (formerly Amphibolurus) ornatus, with a fall of two degrees Celsius in the mean body temperature selected behaviourally in a photo-thermal gradient. The placement of an electrolytic lesion in the base of the hypothalamus, designed to eliminate secretion of the neuropeptide arginine vasotocin (AVT), did not affect the lizards' thermoregulatory behaviour and their Preferred Body Temperature (PBT) was not significantly different from that of unoperated controls. Saline loading, however, did not induce thermal depression in these tract-operated individuals and their PBT was significantly higher than that of salt-loaded intact individuals. When AVT was injected into operated, salt-loaded, animals, however, thermal depression was observed, supporting the hypothesis that thermal depression brought about by hypernatraemia is mediated through the action of AVT. AVT similarly significantly depressed the PBT of injected intact individuals by 3.2 degrees C when compared with hydrated controls. Immunostaining for AVT confirmed that the lesions placed in the region of the median eminence virtually eliminated AVT located in the neurohypophysial tract, and the pars nervosa. This is the first report of an effect of this peptide on behavioural thermoregulation in a lizard.

Analysis of Variance↗

Involvement of arginine vasotocin in reproductive events in the male newt Cynops pyrrhogaster.

Effects of arginine vasotocin (AVT) on reproductive events such as courtship behavior, pheromone release, and spermatophore discharge were investigated in the male newt Cynops pyrrhogaster. AVT enhanced the incidence and frequency of androgen-induced courtship behavior. In this case, AVT was likely to act centrally because the behavior was evoked with a much smaller amount of AVT when the hormone was administered intracerebroventricularly than when given intraperitoneally. Involvement of endogenous AVT in spontaneously occurring courtship behavior was also evidenced by the fact that administration of a V1 (vasopressor) receptor antagonist, [d(CH2)5(1), Tyr(Me)2, Arg8-vasopressin] suppressed the expression of the courtship behavior. The water in which AVT-treated males had been kept showed considerable female-attracting activity as compared with the water in which saline-injected males had been kept. Moreover, the content of sodefrin, a female-attracting pheromone in the abdominal gland, was decreased by the intraperitoneal injection of AVT, suggesting that the neurohypophyseal hormone stimulated the release of sodefrin from the abdominal gland into the water. AVT induced contraction of the excised abdominal gland concentration-dependently, and, again, the V1 receptor antagonist suppressed the AVT-induced contraction. Thus, we concluded that AVT induces the pheromone discharge, acting peripherally on a contractile structure of the abdominal gland. AVT was also found to induce spermatophore deposition in the male kept in the absence of the female. Administration of the V1 receptor blocker to the sexually developed males suppressed the spermatophore deposition. All these results indicate the involvement of AVT in reproductive events acting centrally and peripherally.

Animals↗

Vasotocin treatment inhibits courtship in male zebra finches; concomitant androgen treatment inhibits this effect.

Zebra finches evolved in arid areas of Australia. Their reproduction is stimulated by water availability, which is unpredictable. Cheng (Poult. Sci. Rev. 5 (1993) 37) hypothesized that the primary mechanism controlling reproduction in species relying on unpredictable cues should be inhibitory. The onset of stimulatory environmental conditions terminates the inhibition, allowing rapid initiation of reproduction. As the primary hormone regulating water balance in birds, arginine vasotocin (AVT) appears a likely candidate to modulate reproduction in finches. Drought conditions cause sustained AVT release, which in other species inhibits androgen production. To determine whether increased AVT inhibits reproductive behavior, intact males were tested with females and divided into three groups matched for courtship behavior. Osmotic minipumps containing (a) saline, (b) 264 ng AVT, or (c) 1320 ng AVT in saline were implanted subcutaneously and males tested 48 h later. AVT-treated males socialized with females, but the high dose significantly reduced singing and courtship displays. To determine whether AVT acted by depressing androgen secretion, additional males were given subcutaneous androgen implants and divided into two groups matched for courtship behavior. Males were then implanted with minipumps containing (a) saline or (b) the high AVT dose. Males treated with AVT plus androgen showed no deficits in courtship behavior. These data suggest that AVT secretion during periods of drought may inhibit reproduction by inhibiting androgen production. Inhibition of reproductive behavior by AVT may be a more general phenomenon. Large quantities of AVT or, in mammals the closely-related peptide vasopressin (VP), are released when animals are stressed, and high levels of AVT/VP may inhibit reproductive behavior. The extremely short half-life of these peptides means that once proximal factors become more favorable, the gonads should rapidly be released from the peptides' inhibitory actions.

Androgens↗