Reproduction and Breeding 1 (2021) 128–135

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Reproduction and Breeding

journal homepage: www.keaipublishing.com/en/journals/reproduction-and-breeding

A review on ghrelin and fish reproduction

Huan Zhong a, Yi Hu a, Fan Yu b, *
a
Hunan Research Center of Engineering Technology for Utilization of Distinctive Aquatic Resources, College of Animal Science and Technology, Hunan Agricultural
University, Changsha, 410128, China
b
Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery
Sciences, Wuxi, 214081, China

A R T I C L E I N F O A B S T R A C T

Keywords: Ghrelin is a multifunctional peptide hormone which dominantly secreted in stomach and intestine. Ghrelin in-
Hormone volves in growth control, food intake, energy balance, and reproductive process. Recent evidences suggested that
Gonad ghrelin also interacts with hypothalamic–pituitary–gonadal axis (HPG axis) and controls gametes maturation. In
Gamete maturation
addition, current clues showed that via regulating ghrelin system (acyl ghrelin: des acyl ghrelin ratio, GOAT, GHS-
Hypothalamic–pituitary–gonadal axis
Diets
R1a), glucose and weight could be regulated promising a potential way for artificial controlling of gonadal
development and gamete maturation. The ghrelin signaling system may be a new target for reproductive oper-
ation in fish artificial propagation and breeding. This review summarizes the recent studies of the function of
ghrelin in fish reproduction and the regulatory methods for ghrelin system.

1. Introduction
Food intake and energy balance are two essential biological processes
in fishes which guarantee sufficient energy for fish growth, reproduction,
and other behaviors to survive [1,2]. Several regulatory networks have
been found to participate in controlling food intake and energy balance,
such as hypothalamic–pituitary–adrenal axis (HPA axis) [3], hypothal-
amic–pituitary–gonadal axis (HPG axis) [4], and brain-gut axis [5]. In
these axes, hormones are dominant factors to control food intake and
energy balance [6,7]. For example, as a key member of HPG axis,
melanin-concentrating hormone (MCH) involves in food intake regula-
tion, which is mainly expressed in pituitary gland [7].
Gonadotropin-releasing hormone (GnRH) as one of the known hormones
secreted by hypothalamus is generally used for inducing fish ovulation,
which also has function in regulation of feeding by interacting with
orexin [8]. Commonly, food intake and energy balance have been
regarded under control of central nervous system (CNS) [9]. Besides to
CNS, enteroendocrine hormones also play a crucial role in regulation of
food intake [10]. Intestinal hormones and neuropeptide hormones such
as ghrelin have been found acting on hypothalamus and limbic system
stimulating appetite [11,12].
Ghrelin was first reported in rat and human stomach which has also
been considered as a growth hormone secretagogue (GHS) by interacting
with its receptor growth hormone secretagogue receptor (GHS-R) [13].
The following clues showed the function of ghrelin in food intake and
energy balance in human and animals [14–16]. Regarding the regulation
of ghrelin on energy homeostasis, abundant studies have been focused on
its role in etiology such as obesity [17], cardiovascular diseases [18], and
diabetes [19]. Additionally, numerous medicines have been developed to
intervene the ghrelin-GHS-R axis to cure these diseases which have ob-
tained good effects [20–22]. Simultaneously, multiple biological func-
tions associated with ghrelin-GHS-R axis have been found [23,24].
Recently, ghrelin reduced the expression of autophagy-related genes in
obesity-associated type 2 diabetes, which was reported to promise a
novel molecular function and promise a potential treatment strategy
[25]. In fishes, ghrelin is a concerned intestinal endocrine hormone and
has potential value for artificial control of organism growth and feed
utilization [26]. It has been shown that ghrelin-GHS-R axis connected
with growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis to
regulate fish growth [27,28]. The communication between
ghrelin-GHS-R axis and HPG axis affects gonadal development of fishes
[29]. Previously, we found that injection of ghrelin could increase sur-
vival rates of tilapia with Aeromonas hydrophila infection [30]. Ghrelin
also has functions in anti-inflammation, regulating insulin release and
glucose metabolism in fishes [31]. Thus, ghrelin is a central factor that
regulates organism growth, food intake, energy homeostasis,
anti-pathogens and autoimmune [26]. These evidences suggest that
digestive tract as the main secretion site of ghrelin is not only a digestive

* Corresponding author.
E-mail address: yuf@ffrc.cn (F. Yu).

https://doi.org/10.1016/j.repbre.2021.07.004
Received 23 May 2021; Received in revised form 13 July 2021; Accepted 26 July 2021
Available online 4 August 2021
2667-0712/© 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
H. Zhong et al. Reproduction and Breeding 1 (2021) 128–135

organ, but also a multifunctional organ. Table 1

Development of germ cells is crucial for lasting of germline and Several studies of the tissue distributions of ghrelin in fishes.
concerned by researchers for fish breeding and farmers [32,33]. Culti- Species Tissue Method References
vation of broodstock could promise mature gametes for breeding. Thus,
Goldfish intestine Northern blot [60]
finding strategies for inducing high-quality broodstock via nutrient Sea bass proximal intestine, stomach, brain real-time [61]
regulation may provide new approach to increase the fertility and fry quantitative
quality [34]. Up to date, the requirement of broodstock has been widely PCR
investigated and the feeding formula as well as additives [35,36]. These Zebrafish ovary, testis, brain, liver, skin, RT-PCR analysis [62]
heart, gill, muscle and gut
new diets improved the effect of broodstock cultivation. Farmed fish are Common foregut, hindgut, spleen and brain RT-PCR [63]
various and single feeding formula and additive may not satisfy the carp
requirement of different species. Therefore, understanding the nutrient Channel high levels in the stomach real-time [64]
needs and its molecular mechanism is important for cultivation of catfish moderate levels in the pancreas quantitative
and gall bladder PCR
broodstock. Digestive tract is the first object for nutrient absorption and
low levels in the hypothalamus,
sensitive to nutrients after feeding. The secreted hormones such as pituitary, gill, muscle, liver,
ghrelin from digestive tract could response to nutrient and act on CNS to spleen, trunk kidney, head kidney,
regulate the behavior of food intake [37]. In addition, ghrelin as key node antierior intestine, middle
factor had multiple physiological functions. With increasing evidences intestine, posterior intestine
Japanese stomach Northern blot [56]
indicating ghrelin plays an important role in fish reproduction, this eel analysis
article provides an overview of the update studies on basic information of Japanese brain, heart, stomach, intestines, RT-PCR analysis [56]
ghrelin, its function in reproduction and potential approach to regulated eel body kidney and head kidney
ghrelin artificially. Seabream stomach RT-PCR [59]
Atlantic stomach (low expression was qPCR [65]
salmon detected by qPCR in pyloric caeca)
2. Ghrelin Grass carp highest in the foregut real-time [66]
moderate in the muscle, liver, quantitative
2.1. Structure and expression hypothalamus, white adipose PCR
tissue, midgut, heart, and pituitary
low in hindgut, spleen, gill
Ghrelin has been regarded as a 28-amino-acid peptide when it was Blunt snout intestine (foregut, midgut, qPCR [54]
first identified in mammalian [38]. This peptide hormone is encoded by bream hindgut), muscle, liver, heart,
ghrelin and obestatin prepropeptide (GHRL) gene [39]. GHRL has four spleen, gill, kidney, pituitary,
exons in human which produces ghrelin and obestatin [40]. GHRL is hypothalamus
transcribed into proghrelin in ribosomes. Then, the proghrelin is acylated
by ghrelin O-acyltransferase (GOAT) in endoplasmic reticulum [41]. red-bellied piranha (Pygocentrus nattereri), ghrelin is a widespread gene
Finally, the acylated proghrelin is transferred into Golgi apparatus via that expresses in brain, pyloric caeca, and intestine [58]. On contrary,
vesicle transporting and then cut into mature ghrelin [42]. The mature ghrelin was only secreted in stomach in black seabream (Acanthopagrus
acylated ghrelin could be transferred into different organs through blood schlegeli) [59]. These results indicated that the expression sites of ghrelin
circulatory system and interacted with specific GHS-R [43]. With large are different depending on species.
amount of ghrelin proteins have been identified, the sequences of amino
acids show diversity in different species. In goldfish (Carassius auratus),
11 different molecular forms of ghrelin were identified [44]. Goldfish is a 2.2. GHRL and ghrelin in different species
species experienced polyploidization [45]. Therefore, it is reasonable to
contain different ghrelin genes in the duplicated genome as tetraploid. We compared the deduced GHRL protein from 7 fishes including 4
The synthesized 12 amino-acid (GTSFLSPAQKPQ) form shows similar species of Cyprinid, 1 species of Siluriformes, 1 species of Salmoniformes
effects and has been used for the function study of ghrelin in vitro [44]. and 1 species of Perciformes (The fishes contain Danio rerio, Ctenophar-
Despite of the diversity of ghrelin mature peptides, the serine in third yngodon idella, Cyprinus carpio, Carassius auratus, Ictalurus punctatus,
amino acid is conserved from fish to mammalian [46]. This residue is the Salmo salar and Sparus aurata). The prepropeptide length is ranged from
site for ghrelin acylation. Acyl ghrelin plays its biological function via 103 to 108 amino acids and the similarities covered from 35.00% to
interacting with GHS-R [47,48]. Interestingly, GHS-R contains two 89.32% (Table 2). Meanwhile, the mature ghrelin was not conversed in
different receptors including GHS-R1a and GHS-R1b. Only GHS-R1a has length either which had 19-22 amino acids in these fishes (Fig. 1A).
function while GHS-R1b is a truncated non-function receptor which Noticeably, the third residues of the mature peptide were serine in all the
could not interact with acyl ghrelin [49–51]. fishes suggesting the conserved sites for acylation [38]. The phylogenetic
Stomach and intestine are the dominant tissues for ghrelin secretion. analysis showed that the ghrelin in vertebrates grouped into five main
As reported in mammals, high expression of ghrelin was found in the clades corresponding to the classification in the evolution. The phylo-
stomach, while low expression of ghrelin was shown in small and large genetic tree indicated that Cyprinidae ghrelin clustered with other teleost
intestines [52]. Some studies suggested that ghrelin could be generated homologues, such as Siluridae and Salmonidae ghrelin (Fig. 1B). These
by CNS [53]. In stomach, gastric X/A-like endocrine cell is the main results suggested that ghrelin had the similar function in the animals. The
secretion cell types for ghrelin production. In the fish without stomach, GHRL proteins in Amphibian, Reptilian, Avian, and Mammalian had less
the ghrelin expressed in intestine [54,55]. However, the origin of the similarity with the GHRL proteins in Teleost which were not clustered
intestinal cells that secreted ghrelin is still blurred. In goldfish, a species together.
lacking stomach, it showed that mucosal cells were the primary synthe-
sizing site for ghrelin by in situ hybridization [51]. Northern blot and 2.3. Ghrelin acylation
RT-PCR analyses suggested stomach had high ghrelin expression and low
expression in other tissues including brain, intestine, kidney, and After translation into proghrelin, the protein is acylated by GOAT and
head-kidney in Japanese eel (Anguilla japonica) [56]. Meanwhile, ghrelin fragmented into mature ghrelin in Golgi apparatus [41]. In the classical
mRNA had high expression in nighttime displaying a daily rhythm [57] theory, des-acyl ghrelin has no biological function because des-acyl
(Table 1). Considering the starving status of fish at night, this finding may ghrelin could not interact with GHS-R [67]. Although the evidences are
also result from the different energy balance in the daily rhythm. In relatively scarce, des-acyl ghrelin also induces food intake, impairs

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Table 2
Similarities (%) of amino acids of prepropeptide from the compared species.
Ictalurus punctatus Carassius auratus Danio rerio
Ictalurus punctatus 100 53.4 55.88
Carassius auratus 53.4 100 74.76
Danio rerio 55.88 74.76 100
Ctenopharyngodon idella 57.84 82.52 84.47
Cyprinus carpio 59.8 82.52 80.58
Salmo salar 49.51 44.12 48.51
Sparus aurata 39.42 35 38.38
orexigenic effect, decreases fat mass and increases muscle regeneration
[68]. Due to the multiple functions of des-acyl ghrelin, Delhanty and his
colleagues proposed that des-acyl ghrelin should be regarded as a sepa-
rate hormone besides of acyl ghrelin [69]. Compared to des-acyl ghrelin,
acyl ghrelin interacts with GHS-R1a to regulate several biological pro-
cesses. This classical pathway is the main functional system for ghrelin.
Thus, as a regulator, GOAT could control ratios of acyl ghrelin/des-acyl
ghrelin, which contribute to regulate the energy balance of organisms
[70]. Unlike ghrelin, GOAT is a wide expression gene in tissues. The two
types of GOAT (GOAT-v1 and GOAT-v2) from goldfish were both highly
expressed in gonad and intestine, but lowly expressed in other tested
tissues [71]. These results showed that GOAT is not only expressed in the
tissues that express ghrelin, suggesting GOAT has extensive functions.
Thus, more studies are needed to elucidate the functional details of GOAT
especially the functions of GOAT in other tissue rather than digestive
tract. Taken together, ghrelin, GOAT and GHS-R1a constitute the ghrelin
system to regulate food intake and energy balance.
3. Ghrelin's function in energy balance and reproduction
3.1. Ghrelin's role in food intake and energy balance
The energy metabolism regulated by ghrelin is mediated by control-
ling of food intake and energy conversion. For food intake, ghrelin and its
receptor stimulate neuropeptide Y (NPY)/agouti-related protein (AgRP)
neurons via interacting with mammalian target of rapamycin complex 1
(mTORC1)/mammalian target of rapamycin complex 1 (S6K1) pathway
in neurons of arcuate nucleus from hypothalamus [72]. The activated
NPY/AgRP neurons express NPY and AgRP to induce appetite [73]. For
energy metabolism, ghrelin system regulates glucose metabolism via
stimulating hepatic glycolysis, decreasing activity of glycogen synthase
kinase, promoting peroxisome proliferator-activated receptor gamma
coactivator 1-α (PGC-1α), and inhibiting insulin secretion [74]. New
studies also reported that ghrelin system regulates lipid metabolism [75].
However, the ghrelin regulated lipid metabolism in fishes have been
rarely reported.
3.2. Ghrelin as a regulator of HPG axis
In fishes, as in other vertebrates, HPG axis is the central axis to control
gonadal development and reproductive behavior [76,77]. In this axis, the
most upstream tissue is hypothalamus. Hypothalamus is a part of brain
secretes GnRH [78]. Via binding to its receptor (GnRHR) on the adeno-
hypophysis by traveling down the anterior portion of pituitary, GnRH
induces the secreting cells to produce follicle-stimulating hormone (FSH)
and luteinizing hormone (LH) [79,80]. After released into blood stream,
FSH and LH could travel to gonad and interacted with their specific re-
ceptors FSHR and LHR, respectively [81]. The FSH and LH signals
stimulate testis and ovary to produce sex steroid hormones such as pro-
gesterone, estradiol, and testosterone [82]. The sex steroid hormones act
on gonads and other tissues to regulate sexual behaviors, gonadal
development, and final ovulation.
In mammalian, several studies reported that ghrelin depressed HPG
axis. Ghrelin decreased fire activity of GnRH neurons in C57BL/6J mice
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Reproduction and Breeding 1 (2021) 128–135
Ctenopharyngodon idella Cyprinus carpio Salmo salar Sparus aurata
57.84 59.8 49.51 39.42
82.52 82.52 44.12 35
84.47 80.58 48.51 38.38
100 89.32 47.52 37.37
89.32 100 46.53 37.37
47.52 46.53 100 57.84
37.37 37.37 57.84 100
[83]. Similarly, in dairy heifers, ghrelin injection suppresses GnRH
induced preovulatory gonadotropin surge [84]. Ghrelin also was proven
that had inhibitory effects on GnRH-induced gonadotropin secretion via
acted on hypothalamic in rat [85]. Meanwhile, ghrelin also acts on pi-
tuitary directly. In human, ghrelin suppresses FSH and LH secretion [86].
These similar suppressive effects of ghrelin on LH secretion were also
found in rat (Rattus norvegicus) [87], ovariectomized rhesus monkey
(Macaca mulatta) [88], and ovariectomized sheep (Ovis aries) [89].
However, in rat, FSH was not changed in vivo and induced in vitro by
ghrelin treatment. In fishes, such as goldfish and common carp (Cyprinus
carpio), ghrelin has been reported as a stimulator for LH releasing
[90–92]. The ghrelin regulated Ca- and Protein kinase C (PKC)-mediated
pathways participate in the upregulation of LH in goldfish [93]. The
different effects of fish and mammalian may due to the different treat-
ment conditions (dosage, time, in vivo or in vitro, etc) and species. GOAT
and GHS-R1a have been shown high expressed in testes and ovaries in
several fishes providing clues of regulatory role of ghrelin system on
gonads in a direct way. Ishikawa and his colleagues found that ghrelin
expressed in human testis by immunohistochemistry [94]. The ghrelin
protein expression was also found in rat testis [95]. In addition, Chicken
(Gallus gallus domesticus) ovary expressed ghrelin mRNA was reported
[96]. Ovarian follicle cells in zebrafish had ghrelin immunoreactivity
signals showing protein expression [96]. In Nile tilapia (Oreochromis
niloticus), no mRNA expression was detected in gonad but specific
expressed in stomach. This study also showed that females had higher
mRNA expression of ghrelin compared to males [97]. Thus, ghrelin ex-
presses in testis and ovary depends on species, developmental stage, and
sex. Meanwhile, the reported evidences indicated that ghrelin may act on
testis and ovary directly [98]. Recent studies also showed that ghrelin
could be regulated by hormones from HPG axis [99,100]. All these clues
suggest that ghrelin and HPG axis constitute a network to co-regulate
reproductive activities in fishes (Fig. 2).
3.3. Other mechanism of Ghrelin's role in reproduction
The effects of ghrelin on reproduction could also be mediated by
other mechanisms beside regulating HPG axis. The bovine ghrelin affects
AKT Serine/Threonine Kinase 1 (Akt1) and extracellular signal-regulated
protein kinase (ERK1/2) pathways of oocytes with different effects
depending on the treated time [101]. Another study suggested that
ghrelin accelerated the maturation of oocyte in vitro exerting a specific
and direct role [102]. In zebrafish, ghrelin could inhibit basal and MIH
induced stage IV germinal vesicle breakdown (GVBD) [103]. Intraperi-
toneal injection with human ghrelin increased number of mature ovarian
follicles but reduced the diameters of the oocyte in Barbus sharpeyi [104].
These results indicate that the effects of ghrelin on gametes maturation is
not only mediated by HPG axis. Unfortunately, the details of the direct
effects of ghrelin on follicle developments are still not systematically
investigated. Two potential mechanisms may be participated by ghrelin
in the gonads: 1. Ghrelin directly interacts with GHS-R1a in gonads and
switch on downstream pathways such as Akt1 and ERK1/2 pathways to
control the gonad maturation; 2. As a key regulator for energy meta-
bolism, ghrelin control the energy utilization for gonadal development
(Fig. 2).
H. Zhong et al. Reproduction and Breeding 1 (2021) 128–135

Fig. 1. Phylogenetic analysis of preproghrelin in vertebrates. A. Multiple sequence alignment of preproghrelin peptides of 7 fishes. The red box showed mature ghrelin
peptide. B. Neighbor Joining phylogenetic tree in vertebrates based on the amino acid sequences by MEGA4 (http://www.megasoftware.net/). The numbers at the
branches were bootstrap values (1000 repetitions). All the sequences were downloaded from NCBI GenBank database: Danio rerio: NP_001077341.1; Cyprinus carpio:
BAF95542.1; Sinocyclocheilus anshuiensis: XP_016314450.1; Ctenopharyngodon idella: AFI98391.1; Carassius auratus: XP_026069130.1; Anabarilius grahami:
ROL50687.1; Labeo rohita: BAX76678.1; Astyanax mexicanus: XP_022531474.1; Ictalurus punctatus: NP_001187244.1; Salmo salar: NP_001133057.1; Clupea harengus:
XP_031423948.1; Oncorhynchus mykiss: XP_021423083.2; Pangasianodon hypophthalmus: XP_026801445.2; Piaractus brachypomus: AJO68701.1; Salvelinus alpinus:
XP_023851722.1; Silurus meridionalis: AER12037.1; Tachysurus fulvidraco: XP_026999190.1; Acanthopagrus latus: XP_036957504.1; Anarrhichthys ocellatus:
XP_031704024.1; Morone saxatilis: XP_035517613.1; Anguilla anguilla: XP_035237098.1; Lepisosteus oculatus: XP_015202865.1; Sparus aurata: XP_030274358.1; Bufo
japonicus: BAM29298.1; Bufo bufo: XP_040264397.1; Rhinatrema bivittatum: XP_029453476.1; Dermochelys coriacea: XP_038265762.1; Trachemys scripta elegans:
XP_034632246.1; Nothoprocta pentlandii: NWX88017.1; Gallus gallus: NP_001001131.1; Homo sapiens: NP_001128413.1; Mus musculus: NP_001273333.1; Rattus nor-
vegicus: NP_067701.1.

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Fig. 2. Representation of the ghrelin-HPG axis crosstalk and its role in reproduction. “?” represented the key mechanism that is still under investigation.

4. Regulation of ghrelin system in reproduction regulation of ghrelin system promises a potential approach to artificial
control of fish reproduction.
4.1. Agonists and inhibitors injection
4.2. Regulation of ghrelin system via diets
Until now, peptide hormones are well investigated because they
could be key targets for regulating biological process. To intervene
Diet control is an easier way to operate in fish farming. Diet regulated
growth performance, energy metabolism, diseases, gonadal develop-
function could be changed by the feeding dosage, feeding times and di-
ment, and reproductive behaviors, several agonists and inhibitors for the
etary formula which contains multiple variables. Therefore, it is easy to
hormones along with their regulated factors and receptors have been
change the feeding strategies. For example, ketogenic diet decreased
developed. In application of aquaculture, the artificial control of HPG
ghrelin and des-acyl ghrelin plasma levels [110]. As a sensor of food
axis is an example. Human chorionic gonadotropin (hCG), luteinizing
supply, abundant feeding inhibits and starvation stimulates ghrelin sys-
hormone-releasing hormone agonist (LHRH-A) and domperidone (DOM)
tem. However, feeding conditions (feeding, fasting, fasting-refeeding)
injections change the activities of HPG axis to regulate gonadal matu-
affects multiple molecular pathways and biological processes. Intake of
ration and ovulation which have made a great economic value for world
medium-chain fatty acids could increase the acyl modification of ghrelin
aquaculture [105]. Several agonists and inhibitors have been developed
[111]. This finding gave a new thought to control levels of acyl ghrelin
in recent years. The original intention for developing these factors were
via changing feeding formula. Caprylic acid (C8:0) supplement might
controlling human diseases such as diabetes and obesity. Injection with
provide octanoyl-CoA for ghrelin acylation and changed the ratios of acyl
ghrelin have been used for studying its function. Meanwhile, ghrelin has
ghrelin/des-acyl ghrelin [112]. Acyl ghrelin inhibited meiosis of bovine
also been employed to control growth by inducing GH releasing. Acyl
oocytes and resulted in simultaneous maturation of oocytes [101].
ghrelin is the dominate part of ghrelin to play the function, thus, syn-
Although the mechanism of bovine oocyte maturation may be different
thesized acyl ghrelin is also used for stimulating appetite of goldfish
from fish, the approach of caprylic acid intake changes acyl ghrelin levels
[106]. The synthetic peptide (growth hormone releasing peptide 6
may also be used for regulating maturation of fish gametes.
(GHRP-6)) and non-peptide (capromorelin) GHS-R agonists were deter-
mined as regulators for gastric motor [107]. Inhibitors of ghrelin and its
5. Conclusion
receptors were also used for controlling adipogenesis and diabetes. In
addition, GOAT antagonist GO-CoA-Tat, a peptide-based bisubstrate
Ghrelin system is a critical system for energy metabolism and food
analog was designed to depress production of acyl ghrelin [108] which
intake which also plays a key role in fish reproductive processes. Ghrelin
was used for controlling glucose and weight. In male ob/ob mouse which
interacting with hormones from HPG axis representing ghrelin-HPG axis
is an animal model of type II diabetes, inhibition of ghrelin led to improve
crosstalk to regulate gonadal development and gamete maturation.
the phenotypes of reproduction [109]. In contrast to mammalian, ghrelin
However, the gene regulatory networks and functional details are far
in several fishes has positive effects on gonadal maturation. However, the
from systematically understood. As a key node for energy balance and
different effects in animals derived by ghrelin are still needed to be
HPG axis, the feedback of sexual hormones on ghrelin in fish is unveiled.
elucidate to guide the operation. As key regulator system, hormonal
Meanwhile, the energy metabolism regulated by ghrelin during

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reproductive cycles in fish is not investigated yet. By elucidation these
questions, it is possible to precisely control reproductive cycles, gametes
maturation, and ovulation of fishes.
Declaration of competing interest
The authors declare no competing financial interests.
Acknowledgments
This research was supported by National Natural Science Foundation
of China (31760756) and the Natural Science Foundation of Hunan
Province (2021JJ20033).
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