Structural modifications of non-mammalian gonadotropin-releasing hormone (GnRH) isoforms: design of novel GnRH analogues

Lovejoy, David A.; Corrigan, A; Nahorniak, Carol S.; Perrin, Marilyn H.; Porter, John; Kaiser, R.; Miller, Charleen; Pantoja, D Soto; Craig, A. Grey; Peter, Richard; Vale, Wylie; Rivier, Jean; Sherwood, Nancy M.

doi:10.1016/0167-0115(95)00116-6

Cited by 17 publications

(5 citation statements)

References 44 publications

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“…In order to increase LH releasing potency, different agonists have been synthesized, mainly by substitutions in the sixth residue in combination with a C terminal ethylamine group (Karten & Rivier, 1986). These structural modifications can affect physiological events, such as enzymatic degradation, receptor binding and activation, plasma protein binding and renal clearance rates (Lovejoy et al ., 1995). In goldfish Carassius auratus (L.) it was demonstrated that these structural modifications in positions six and 10 increased receptor binding affinity and biological activity at the pituitary level (Habibi et al ., 1989).…”

Section: Introductionmentioning

confidence: 99%

Relative potency of the forms of GnRH and their analogs on LH release in sea bass

Forniés

Carrillo

Mañanós

et al. 2003

Journal of Fish Biology

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The in vivo and in vitro potency of native and modified forms of gonadotropin releasing hormone (GnRH) to release luteotropic hormone (LH) was studied in sea bass Dicentrarchus labrax in particular the hypothalamic fish‐specific sea bream GnRH form (sbGnRH) and the general mesoencephalic form chicken GnRH‐II (cGnRH‐II). The potencies of the natives and their analogs (GnRHas) were referred to that of [D‐Ala6, Pro9Net]‐mGnRHa (LHRHa) at equivalent doses. Analogs of the native peptides [D‐Arg6, Pro9Net]‐cGnRH‐II, [D‐Ala6, Pro9Net]‐cGnRH‐II, [D‐Trp6, Pro9Net]‐sbGnRH and [D‐Ala6, Pro9Net]‐sbGnRH were effective in inducing in vivo LH release (at 15 µg kg−1 body mass), exhibiting longer lasting activity than their corresponding native forms. Injection of sbGnRH and cGnRH‐II provoked a small but significant peak of circulating LH at 1·5 h after treatment (a.t.) decreasing down to basal levels at 4 h a.t. [D‐Arg6, Pro9Net]‐cGnRH‐II, [D‐Ala6, Pro9Net]‐cGnRH‐II and [D‐Ala6, Pro9Net]‐mGnRHa evoked a higher and a more sustained elevation of LH, peaking at 12 h a.t. and returning to basal levels between 48 and 72 h a.t. [D‐Trp6, Pro9Net]‐sbGnRH and [D‐Ala6, Pro9Net]‐sbGnRH also induced a significant surge of LH in plasma at 4 h a.t. turning to the basal levels at 24 h a.t. These rises, however, were of less amplitude and duration than the observed after treatment with cGnRH‐II analogs and [D‐Ala6, Pro9Net]‐mGnRHa. The in vitro stimulation of dispersed pituitary cells with the different native and modified forms of GnRH resulted in a dose‐dependent increase in the quantity of LH released at 24 h a.t. [D‐Arg6, Pro9Net]‐cGnRH‐II and [D‐Ala6, Pro9Net]‐cGnRH‐II induced the highest response of LH in vitro release followed by salmon GnRH (sGnRH), [D‐Ala6, Pro9Net]‐mGnRHa and [D‐Trp6, Pro9Net]‐sbGnRH. The lowest activity was exhibited by sbGnRH. Collectively, the in vitro biological activity (compared by their EC50) can be ordered as follows: [D‐Arg6, Pro9Net]‐cGnRH‐II > [D‐Ala6, Pro9Net]‐cGnRH‐II > sGnRH > [D‐Ala6, Pro9Net]‐mGnRHa > [D‐Trp6, Pro9Net]‐sbGnRH > [D‐Ala6, Pro9Net]‐sbGnRH > cGnRH‐II > sbGnRH.

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Section: Introductionmentioning

confidence: 99%

Relative potency of the forms of GnRH and their analogs on LH release in sea bass

Forniés

Carrillo

Mañanós

et al. 2003

Journal of Fish Biology

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“…(33) demonstrated that both sGnRH and cGnRH‐II are differentially regulated during natural ovulation and spawning, and suggested that the periovulatory LH surge is primarily regulated by sGnRH, whereas cGnRH‐II regulates spawning behaviour. Nevertheless, both forms of GnRH have been shown to stimulate LH release from goldfish pituitary fragments (34), and to increase circulating LH in goldfish in vivo (22, 35). In pituitary cells prepared from sexually regressed females, cGnRH‐II elicits a biphasic and more prolonged (peak and plateau) LH response, whereas sGnRH elicits a monophasic response of shorter duration (peak only) (36).…”

Section: Discussionmentioning

confidence: 99%

Dopamine D₁Receptor Blockage Potentiates AMPA-Stimulated Luteinising Hormone Release in the Goldfish

Popesku

Mennigen

Chang

et al. 2011

Journal of Neuroendocrinology

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Previous microarray analyses of the goldfish hypothalamus led us to hypothesise that dopamine could potentially inhibit the excitatory effects of glutamate on luteinising hormone (LH). Post-spawning female goldfish were pre-treated (-4.5 h) with either saline (C; control), SCH 23390 (S; D(1) -receptor antagonist) or sulpiride (L; D(2) -receptor antagonist), followed by an i.p. injection, at -0.5 h, of saline or the glutamate agonist AMPA (A, SA or LA). Blood, hypothalamus and telencephalon tissues were collected. Serum LH was not affected in the S, L, A, or LA groups relative to control as determined by radioimmunoassay. The SA group, however, showed a 289% (P<0.0005) increase in serum LH compared to either treatment alone or control. Real-time reverse transcriptase-polymerase chain reaction identified the mRNAs for ionotropic (Gria2a, Gria4) glutamate receptor subunits, activin βa, isotocin, and cGnRH-II as being significantly affected by some of the treatments. The same experiment conducted with sexually-regressed female fish showed a very different LH profile, indicating that this mechanism is seasonally-dependent. We also show that i.p. injection of 1 μg/g isotocin was able to increase LH levels by 167% in sexually regressed female fish relative to controls. Taken together, these results demonstrate that blockage of the D(1) receptor primes post-spawning goldfish for AMPA-stimulated LH release, and provides further insights into the central regulation of reproduction.

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“…GnRH, which acts on the pituitary via direct innervation, stimulates the secretion of gonadotropins (GtH) that act on the gonad resulting in the production of steroids and prostaglandins (Rottmann et al, ). Since the discovery of the GnRH decapeptide and its associated role in the HPG axis, a large body of research has focused on optimization of dose, identification of active variants and development of potent analogues (Alok, Talwar, & Garg, ; Bosma, Rebers, Dijk, Willems, & Goos, ; DiMaggio et al, ; DiMaggio, Broach, & Ohs, ; Forniés et al, ; Lovejoy et al, ; Mikolajczyk et al, ; Mylonas, Hinshaw, & Sullivan, ; Ngamvongchon, Rivier, & Sherwood, ; Podhorec & Kouril, ; Prayogo, Wijayanti, Sulistyo, & Sukardi, ; Quiniou, Bosworth, Chatakondi, & Oberle, ; Sahoo, Giri, & Sahu, ; Szabó, Radics, Barth, & Horváth, ; Taufek, Harmin, & Christianus, ; Zohar et al, ). One advantage of using GnRH is that it occurs earlier in the hormonal cascade stimulating the release of endogenous stores of GtH and facilitating the contribution of supplementary endocrine factors such as prolactin, thyroid hormones, insulin like growth factors and growth hormone (Podhorec & Kouril, ).…”

Section: Introductionmentioning

confidence: 99%

“…Variants within the systems are named after the organism they were first described in, with mGnRH I found initially in mammals, cGnRH II in chickens and sGnRH III in salmon (Kah et al, ). With the discovery of GnRH came laboratory synthesized analogs targeting substitutions of amino acid bonds that were prone to enzymatic degradation (Lovejoy et al, ). Alterations at these specific positions have made GnRH analogs (GnRHa) more potent as induced spawning aids by increasing binding affinity and prolonging the duration of activity while in circulation (Taufek et al, ; Zohar & Mylonas, ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of cGnRH IIa for induction spawning of two ornamental Epalzeorhynchos species

et al. 2019

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The administration of exogenous hormones for induction spawning of captive fish is a common practice throughout the finfish aquaculture industry. Induced spawning protocols for ornamental cyprinids commonly rely on sGnRH IIIa, commercially available as Ovaprim. In this study, the efficacy of an alternative spawning aid, cGnRH IIa, was evaluated relative to Ovaprim, in two commonly cultured ornamental Cyprinids: the Redtail Sharkminnow Epalzeorhynchos bicolor and the Rainbow Shark E. frenatum. Broodstock of each species were injected with either a positive control (0.5 µl/g Ovaprim), a negative control (propylene glycol) or one of three doses of cGnRH IIa (50, 100, or 200 µg/kg). Following spawning aid injection, ovulation success, fecundity, fertilization success, embryo diameter, hatch success and larval notochord length were evaluated. Ovulation success (82 ± 8%) was statistically similar to the positive control group for all experimental doses of cGnRH IIa in E. bicolor, while 50 and 100 µg/kg cGnRH IIa doses resulted in significantly higher ovulation success (100.0% and 83.0% respectively) than the positive control (17.0%) in E. frenatum. All other parameters did not vary significantly among treatments. These results indicate cGnRH IIa can be successfully used as a spawning aid in both species.

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Structural modifications of non-mammalian gonadotropin-releasing hormone (GnRH) isoforms: design of novel GnRH analogues

Cited by 17 publications

References 44 publications

Relative potency of the forms of GnRH and their analogs on LH release in sea bass

Relative potency of the forms of GnRH and their analogs on LH release in sea bass

Dopamine D₁Receptor Blockage Potentiates AMPA-Stimulated Luteinising Hormone Release in the Goldfish

Evaluation of cGnRH IIa for induction spawning of two ornamental Epalzeorhynchos species

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Structural modifications of non-mammalian gonadotropin-releasing hormone (GnRH) isoforms: design of novel GnRH analogues

Cited by 17 publications

References 44 publications

Relative potency of the forms of GnRH and their analogs on LH release in sea bass

Relative potency of the forms of GnRH and their analogs on LH release in sea bass

Dopamine D1Receptor Blockage Potentiates AMPA-Stimulated Luteinising Hormone Release in the Goldfish

Evaluation of cGnRH IIa for induction spawning of two ornamental Epalzeorhynchos species

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Dopamine D₁Receptor Blockage Potentiates AMPA-Stimulated Luteinising Hormone Release in the Goldfish