What is gnih
TNgc: terminal nerve ganglion cells. Figure 4. Double-labeling immunofluorescence in parasagittal brain sections of 27 days post-hatching C. In C , a merge image of A,B is presented. Immunoreactive cell somata are indicated by arrows and some representative fibers appear marked by arrowheads.
Co-localization is indicated by asterisks. For example, Moussavi et al. Similar effects of GnIH peptides were demonstrated in Amphiprion melanopus 46 and in Astyanax altiparanae Although these statements have been mostly established in birds and mammals 80 , 81 , there is evidence that a similar mechanism could be operating in teleosts 34 , 55 , 82 , These discrepancies could be due to differences in sexual stage, route of administration, sampling times and brain regions analyzed.
Also, based on studies performed in birds and mammals, it has been proposed that GnIH could indirectly modulate the expression and activity of brain aromatase regulating estradiol levels locally [for review see 79 ].
According to anatomical and physiological results presented in this section, it must be emphasized that GnIH interaction with GnRH occurs in fish, and either directly or indirectly GnIH can stimulate or inhibits hypothalamic-pituitary axis depending on the reproductive state of individuals.
As Sandvik et al. The few studies addressing GnIH ontogeny show that this peptide is not an exception. To date, there are only four studies analyzing the GnIH expression pattern during fish development, showing that this peptide is detected from early developmental stages 33 , 50 , 51 , In zebrafish gnih and gnih-r transcripts were detected from 1-day post-fertilization dpf prime-5 stage or blastula stage, respectively; however, in this study, no temporal variations in the expression were evaluated In sea bass, gnih and gnih-r transcripts were detected from 5 dpf, and although the authors did not quantify the expression in stages prior to hatching, two temporal increases in the gnih messengers were observed: one from 5 days post-hatching dph to 25 dph, when the larva starts exogenous feeding and the gonad is still undifferentiated, and the other by dph during the onset of gonadal differentiation Studies performed in C.
As we previously mentioned, in different species one or more GnIH cell clusters were observed apart from that of NPPv. The spatial-temporal expression pattern of these nuclei could suggest different origins or functions during development. For example, in the Indian major carp, GnIH cells were observed in the NPPv and in the olfactory system epithelium and bulb at hatching. This mentioned area showed no GnIH-ir in adults, suggesting a role of these cells during development By contrast, in C.
The cells in the NOR increase in number from 5 dph, coinciding with the time when larvae start to feed exogenously, and continue to increase in number during the development and differentiation of gonadal primordia. In the same direction, it was observed an increase of NPPv cell number during the development and differentiation of the gonadal primordia. Based on these results, it is suggested that GnIH could be involved in the onset of feeding and gonadal development or sex differentiation in teleosts.
This new concept is supported by the variations of gnih and gnih-r levels in sea bass and C. On the other hand, during development GnIH fibers innervate different brain regions 33 , Particularly in C. Considering that GnRH1 fibers were detected at 30 dph 85 , we could speculate a shift in the neuroendocrine control of pituitary function occurring before gonadal differentiation. The fact that no GnIH fibers innervating the pituitary gland were detected in adults of this species 25 , could imply that this neuropeptide would act differently in larvae and adults.
Biotic and abiotic factors, especially temperature and photoperiod, are critical features that could irreversibly affect different biological aspects during development.
Even though the neuroendocrine system integrates environmental information, little is known about its development and how it is altered by these factors. For example, low or high incubation temperatures during early developmental stages determine different sex ratio of pejerrey and sea bass larvae 86 , 87 indicating that the reproductive axis, at some point, has been altered.
To our knowledge, only one study reported the effect of temperature and photoperiod on GnIH system during development In this study, sea bass reared at high temperature, showed a decrease in the expression of gnih and gnih-r , suggesting that this neuropeptide could be involved in the reported effect of temperature on sex differentiation. Moreover, a seasonal shift in a daily variation of GnIH system related to the reproductive season was demonstrated, indicating the influence of the photoperiod on this system In summary, GnIH in fish development is an almost unexplored area, so more studies are needed in order to further elucidate its role at this particular stage.
Since the discovery of GnIH, most studies have analyzed the effect of this peptide on the reproductive axis, leaving aside their possible role in the regulation of other functions. In this sense, neuroanatomical localization studies showed in all fish species analyzed that GnIH fibers are broadly distributed along the nervous system, not only in the preoptic-hypothalamic area but also in the retina-optic tract and midbrain, suggesting a potential role of GnIH as neuromodulator or neurotransmitter.
It is important to highlight that in this species a cluster of GnIH cells was observed in the midbrain innervating sensory-motor areas On the other hand, there is increasing evidence regarding the effect of GnIH on the synthesis and release of GH 25 , 26 , 57 , 75 , 76 , Usually, after GnIH administration different responses on the GH synthesis and release were observed depending on the species or the experimental approach.
However, icv administration of GnIH decreased gh in sea bass 76 , whereas intraperitoneal administration of GnIH did not affect GH release in tilapia However, also concerning to GH regulation, a clear dependence on the reproductive status and on the experimental approach was observed in goldfish NPY has been implicated in the modulation of gonadotropin release, but also in the regulation of feeding and growth 38 , Since GnIH cells are observed in these regions, it is suggested that this neuropeptide could establish a crosstalk among growth, feeding, and reproductive axes.
In conclusion, although the effects of GnIH on reproduction are very clear in birds and mammals, there are still some inconsistencies in fishes that should be addressed soon. Because of our attempt to generalize GnIH function, it is possible that different modes of action or other roles beyond reproduction are leaving aside in fishes. Moreover, as reproduction is a complex event that involves the integration of internal and external cues, it is possible that GnIH acts as a link among them.
Interestingly, recent mutation studies for reproductive neuroendocrine factors have shown that, contrary to mammals, kisspeptin, and GnRH null fish can reproduce normally, suggesting a compensatory multifactorial neuroendocrine control of reproduction 93 — Notably, they found an up-regulation of different neuropeptides involved in the control of reproduction in zebrafish including GnIH According Marvel et al. Further studies are still required in order to clarify the role of GnIH in teleosts including its involvement in development, a key stage that strongly impacts on adult biology.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We thank Dr. Daniela I. Federico Obertello for their valuable contributions. A novel avian hypothalamic peptide inhibiting gonadotropin release. Biochem Biophys Res Commun. A journey through the gonadotropin-inhibitory hormone system of fish. Front Endocrinol. Review: structure, function and evolution of GnIH.
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Because of its action on cultured pituitary in quail, it was named gonadotropin-inhibitory hormone GnIH. GnIH decreases gonadotropin synthesis and release, inhibiting gonadal development and maintenance. GnIH actions and interactions with GnRH seem common not only to several avian species, but also to mammals. Thus, GnIH is considered to have an evolutionarily conserved role in controlling vertebrate reproduction, and GnIH homologs have also been identified in the hypothalamus of mammals.
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