Gonadotropin Releasing Hormone (GnRH)

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Gonadotropin Releasing Hormone (GnRH)
Introduction:
Gonadotropin-releasing hormone (GnRH), also known as Luteinizing-hormone-releasing
hormone (LHRH) and luliberin, is a trophic peptide hormone responsible for the release of
follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary.
GnRH is synthesized and released from neurons within the hypothalamus. The peptide belongs
to gonadotropin-releasing hormone family.
Release of GnRH:
Several elements are necessary for the normal release of and response to GnRH: migration of
the secretory neurons via the proper route to the proper location must take place in the
developing embryo and secretion must occur in a pulsatile fashion in response to
neuroendocrine inputs and sex steroids.
GnRH Structure in Fish:
GnRH in fish, as in other vertebrates, is a ten-amino acid peptide made primarily in nerve cells
in the brain. In addition, GnRH peptides have been reported in ovary and testis of fish and in
ovary, testis, mammary gland and placenta of mammals. The structure of GnRH in jawless fish,
cartilaginous fish and bony fish has been determined to date primarily by protein chemistry and
molecular biology.
Expression of GnRH in Fish Brain:
In fish brain, GnRH is expressed very early in development as GnRH neurons are born and
migrate to form populations in three to four general regions: the preoptic area that innervates
the pituitary, the midbrain, the terminal nerve, as well as other areas in the forebrain. In some
fish species, cells congregate into more distinct populations, whereas in other species the cells
tend to form a weakly linked continuum of neurons in most of the areas represented. The
notable exception to this is midbrain neurons, which typically form a discrete population.
GnRH Protein in Fish Gonads:
The presence of GnRH mRNA transcripts in fish gonads supports a potential paracrine role for
GnRH in fish reproduction, whereas the presence of mature peptide solidifies that role. Since
gonadal GnRH cDNA has been demonstrated in a number of vertebrate species, one might
expect to find the translated mature peptide product in the gonad, perhaps at levels that
coincide with the GnRH gene expression.

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The presence of GnRH mRNA in gonads does not necessarily indicate the production of GnRH
peptide. GnRH peptide was not detected in the gonads at any time in adult rainbow trout
during their third year leading to spawning even though transcripts for both of the salmon
genes were detected.
GnRH-Receptor Expression in Fish Gonads:
The production of a ligand by peripheral tissues requires the presence of a receptor on the
same tissue for GnRH to exert an autocrine or paracrine action. GnRH acts by binding to seven-
trans membrane G protein coupled-receptors on the surface of the target cell, ultimately
activating second-messenger systems on the inside of the cell. The pathways activated by GnRH
receptors.
Binding sites for GnRH have been identified on the ovaries and the testes of a number of fish
species including African catfish, seabream, and lamprey. GnRH receptors have been identified
by Northern analysis or RT-PCR in goldfish testis and ovary, Japanese eel testis, adult rainbow
trout ovary, H. burtoni testis, and African catfish testis and ovary.
Role(s) of GnRH in the Gonads:
The exact role of GnRH in peripheral sites is not well understood. Obviously the function is not
the production of GnRH for the release of gonadotropins from the pituitary. GnRH at a high
concentration stimulated meiotic maturation of follicle-enclosed oocytes in fish. A few studies
have examined defects of GnRH peptide on fish ovary in vitro. A number of GnRH peptides
(sGnRH, cGnRH-I and -II, lGnRH-I and -III, and mGnRH) each stimulate goldfish oocyte meiosis,
but block gonadotropin-induced meiosis and testosterone production.
Effects on behavior:
GnRH production/release is one of the few confirmed examples of behavior influencing
hormones, rather than the other way around. Cichlid fish that become socially dominant in turn
experience an upregulation of GnRH secretion whereas cichlid fish that are socially subordinate
have a down regulation of GnRH secretion. Besides secretion, the social environment as well as
their behavior affects the size of GnRH neurons. Specifically, males that are more territorial
have larger GnRH neurons than males that are less territorial males. Differences are also seen in
females, with breeding females having smaller GnRH neurons than controls females.
Conclusion:
A considerable amount of experimental research is needed to verify whether the consensus
sites are functional in fish. Ideally, regulatory regions need to be compared for GnRH genes in
the three groups in species throughout evolution. Already a number of consensus sites have
been noted between human GnRH genes and salmon or tunicate GnRH genes. It is also possible
that the response elements within the promoters may be somewhat different in tunicates, fish
and mammals.

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References:
 Campbell RE, Gaidamaka G, Han SK, Herbison AE (June 2009). "Dendro-dendritic
bundling and shared synapses between gonadotropin-releasing hormone neurons".
Proc. Natl. Acad. Sci. U.S.A. 106 (26): 10835–40. doi:10.1073/pnas.0903463106. PMC
2705602. PMID 19541658.
 Adams BA, Tello JA, Erchegyi J, Warby C, Hong DJ, Akinsanya KO, Mackie GO, Vale W,
Rivier JE and Sherwood NM (2003). Six novel gonadotropin-releasing hormones are
encoded as triplets on each of two genes in the protochordate, Ciona intestinalis.
Endocrinology 144: 1907–1919
 Higa M, Kitahashi T, Sasaki Y, Okada H and Ando H (1997). Distinct promoter sequences
of two precursor genes for salmon gonadotropinreleasing hormone in masu salmon. J.
Mol. Endocrinol. 19: 149–161.
 von Schalburg KR and Sherwood NM (1999). Regulation and expression of
gonadotropin-releasing hormone gene differs in brain and gonads in rainbow trout.
Endocrinology 140: 3012–3024.
 Grober MS, Myers TR, Marchaterre MA, Bass AH and Myers DA (1995). Structure,
localization, and molecular phylogeny of a GnRH cDNA from a paracanthopterygian fish,
the plainfin midshipman (Porichthys notatus). Gen. Comp. Endocrinol. 99: 85–99.