Functional Evidence Regarding Receptor Subtypes Mediating the Actions of Native Gonadotropin-Releasing Hormones (GnRH) in Goldfish, Carassius auratus

Murthy, C.K.; Peter, Richard

doi:10.1006/gcen.1994.1062

Cited by 26 publications

(14 citation statements)

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“…8d-0-These results suggest that the structure-activity rela tions of GnRH receptors on gonadotrophs and somato trophs in goldfish are different. In support of this, in an earlier study in goldfish, (Ac-A-TPro1, 4FD-Phe2, DTrp3-6)-sGnRH (analog C) acted as a 'true' antagonist on GTH-II release, but stimulated GH release on its own [22,24], In contrast, [Ac-D(2)-Nal', 4FD-Phe2, D -Trp\ DArg6]-mGnRH (analog F) strongly enhanced GTH-II re lease, but weakly inhibited GH release [22,24]. Results from other GnRH structure-activity studies in goldfish indicate that the requirements for superactive GnRH ago nists for GTH-II and GH are also different [2,10], Analog L, under both 2-min pulse treatment and 30-min prolonged exposure, stimulated GTH-II release in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 49%

“…Interestingly, some mammalian GnRH antagonists differentially regulated GTH-II and GH release. (Ac-A3-Pro', 4FD-Phe2, D-Trp3, D-Arg6)-mGnRH (analog F of [22]) stimulated GTH-II, but not GH release [22,24] [22]), a potent GnRH antagonist in mammals [21], weakly stimu lated GTH-II release, but strongly suppressed GH release from the perifused pituitary fragments. In order to further characterize the differential actions of analog L on GTH-II and GH release in goldfish, we have studied its doserelated nature of actions on GTH-II and GH release, and specificity of inhibition of native GnRH actions on GTH-II and GH release.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Actions of a Mammalian Gonadotropin-Releasing Hormone Antagonist on Gonadotropin-ll and Growth Hormone Release in Goldfish, <i>Carassius auratus</i>

et al. 1994

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In goldifish the two native forms of gonadotropin-releasing hormone (GnRH), salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), stimulate both gonadotropin-II (GTH-II) and growth hormone (GH) release. Modifications of GnRH structure at positions 1, 2, 3, and 6 often result in an antagonist in goldfish, an observation well documented in mammalian studies. In a preliminary study in goldfish, a mammalian GnRH antagonist, [Ac-D(2)Nal¹, 4Cl-D-Phe², D(3)-Pal^3,6, Arg⁵, D-Ala¹⁰]-mGnRH (analog L) weakly stimulated GTH-II release, and strongly inhibited GH release. The objectives of the present study were to study the dose-related actions of analog L on GTH-II and GH release in the goldfish, the specificity of inhibition of native GnRH actions, and to test whether analog L can act directly on goldfish pituitary cells. In a goldfish pituitary fragments perifusion system, analog L at different concentrations, given as 2-min pulses or as 30-min prolonged treatments, stimulated GTH-II and inhibited GH release in a dose-dependent manner. Analog L at 2 µM concentration (45 min) significantly suppressed sGnRH- and cGnRH-II-stimulated GTH-II as well as GH release. Analog L specifically inhibited GnRH-stimulated GH release, without having any significant effects on the GH release induced by either SKF38393, a dopamine Dl receptor agonist, or thyrotropin-releasing hormone. The GTH-II stimulatory and GH-inhibitory actions of analog L were significantly suppressed by a ‘true’ GnRH antagonist (Ac-Δ³-Pro¹, 4FD-Phe², D-Trp^3,6)-mGnRH. Further, analog L stimulated GTH-II release and suppressed GH release from the enzymatically dispersed goldfish pituitary cells, indicating the direct actions of analog L at the pituitary cell level. Analog L also displaced ¹²⁵I-(D-Arg⁶, Pro⁹ NHEt)-sGnRH bound to crude goldfish pituitary membrane preparations in a dose-related manner. In conclusion, contrary to its action as a potent GnRH antagonist in mammals, analog L has GTH-II stimulatory action in goldfish. Analog L by acting via GnRH receptors at the pituitary cell level differentially acts on GTH-II and GH release, suggesting functional differences in the properties of the GnRH receptors on GTH and GH cells. Analog L also specifically inhibits sGnRH and cGnRH-II actions on GTH-II and GH release.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Differential Actions of a Mammalian Gonadotropin-Releasing Hormone Antagonist on Gonadotropin-ll and Growth Hormone Release in Goldfish, <i>Carassius auratus</i>

et al. 1994

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“…In the goldfish, cGnRH-II and sGnRH also act through a single receptor (sub)type on gonadotrophs (Murthy & Peter 1994). However, the GnRHs apparently make use, at least in part, of different signal transduction pathways, exemplified by a difference in the peptides' dependence on extracellular Ca (Chang et al 1993).…”

Section: A Pmentioning

confidence: 99%

Gonadotrophs but not somatotrophs carry gonadotrophin-releasing hormone receptors: receptor localisation, intracellular calcium, and gonadotrophin and GH release

Bosma¹,

Kolk²,

Rebers³

et al. 1997

Journal of Endocrinology

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Gonadotrophs are the primary target cells for GnRH in the pituitary. However, during a limited period of neonatal life in the rat, lactotrophs and somatotrophs respond to GnRH as well. Also, in the adults of a number of teleost fishes (e.g. carp, goldfish, and tilapia but not trout), GnRH is a potent GH secretagogue. In studying hypophysiotrophic actions of the two forms of GnRH present in the African catfish (Clarias gariepinus), chicken GnRH-II ([His5,Trp7,TyrK ] GnRH; cGnRH-II) and catfish GnRH ([His5,Asn8]GnRH; cfGnRH), we have investigated the effects of G nRH on catfish gonadotrophs and somato trophs. G nRH binding was examined by incubating dispersed pituitary cells attached to coverslips with 125I~ labelled [D-Argr\T rp 7,LeuH ,Pro9-Net]GnRH (sGnRHa), a salmon G nRH analogue with high affinity for the G nRH receptor. Following fixation and immunohistochemistry using antisera against catfish LH and GH, 125I-labelled sGnRHa was localised autoradiographically and silver grains were quantified on gonadotrophs and somatotrophs. Specific binding of ' I-labelled sGnRHa was restricted to gonadotrophs. Both cfGnRH andcGnRH~II dose-dependently inhibited I-labelled sGnRHa binding to gonadotrophs. To substantiate the localisation of functional G nR H receptors, the effects of cfGnRH and cG nR H -II on the cytosolic free calcium concentration ([Ca ' were examined in Fura-2-loaded somatotrophs and gonadotrophs. GnRH-induced increases in [Ca2+]i appeared to be confined to gonadotrophs, in which both endogenous GnRHs caused a single and transient increase in [Ca2*]}. The amplitude of this [Ca2+]j transient depended on the G nR H dose and correlated well with the G nR H s1 effect on LH release. In vivo experiments demonstrated that G nR H treatments which markedly elevated plasma LH levels had no effect on plasma GH levels, while a dopamine agonist (apomorphine) significantly elevated plasma GH levels. W e con clude that the two endogenous forms of G nR H in the African catfish are not directly involved in the regulation of the release of GH, suggesting that GnRHs cannot be considered as GH secretagogues in teleosts in general.

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“…Two other GnRH analogs based on native GnRH peptide sequences-[Ac-A 3 -Pro', 4FD-Phe 2 , D-Trp 3 ' 6 ]-sGnRH (analog C of [9]) and [Ac-D(2)Nall, 4C-D-Phe 2 , D-(3)Pal 3 ' 6 ]-cGnRH-II (analog N of [91)-inhibited GTH-II and GH release stimulated by sGnRH and cGnRH-II; however, analog C was found to have GH-releasing actions on its own, indicating that it is not a "true" antagonist to GH release [9,10]. The differential action on GTH-II and GH release by analog C, [Ac-A 3 -Pro', 4FD-Phe 2 , D-Trp 3 , D-Arg 6 ]-mGnRH (analog F [9]), and [Ac-D(2)-Nall, 4C1-D-Phe 2 , D-(3)Pal 3 ' 6 , Arg 5 , D-Ala 0 ]-mGnRH (analog L; C.K.…”

Section: Introductionmentioning

confidence: 88%

Receptor Binding of Gonadotropin-Releasing Hormone Antagonists That Inhibit Release Of Gonadotropin-ll and Growth Hormone in Goldfish, Carassius Auratus1

Murthy

Wong

Habibi

et al. 1994

Biology of Reproduction

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In goldfish, GnRH stimulates gonadotropin-II (GTH-II) and growth hormone (GH) release. The two native forms of GnRH, salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), bind to two classes of GnRH binding sites: high-affinity/low-capacity sites and low-affinity/high-capacity sites. Our previous in vitro perifusion studies of goldfish pituitary fragments showed that [Ac-delta 3-Pro1, 4FD-Phe2, D-Trp3,6]-mGnRH (analog E), [Ac-delta 3-Pro1, 4FD-Phe2, D-Trp3,6]-sGnRH (analog C), and [Ac-D(2)Nal1, 4Cl-D-Phe2, D-(3)Pal3,6]-cGnRH-II (analog N) inhibited both sGnRH- and cGnRH-II-stimulated GTH-II and GH release. Interestingly, analog C stimulated GH release but not GTH-II release. The objectives of the present study were 1) to test the site of action of GnRH antagonists in goldfish, 2) to test the relationship between receptor binding affinity of antagonists and their in vitro inhibitory potencies and apparent duration of action, and 3) to compare the binding characteristics of analog C with its differential action on GTH-II and GH release. As in previous studies, analog E suppressed sGnRH-stimulated GTH-II and GH release from perifused pituitary fragments. Similarly, analog E suppressed both sGnRH- and cGnRH-II-stimulated GTH-II and GH release from perifused dispersed goldfish pituitary cells, indicating the direct action of GnRH antagonists at the pituitary cell level. In the receptor binding studies, analog E displaced 125I-[D-Arg6, Pro9NHEt]-sGnRH (sGnRH-A) from crude goldfish pituitary membrane preparations in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

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Functional Evidence Regarding Receptor Subtypes Mediating the Actions of Native Gonadotropin-Releasing Hormones (GnRH) in Goldfish, Carassius auratus

Cited by 26 publications

References 0 publications

Differential Actions of a Mammalian Gonadotropin-Releasing Hormone Antagonist on Gonadotropin-ll and Growth Hormone Release in Goldfish, <i>Carassius auratus</i>

Differential Actions of a Mammalian Gonadotropin-Releasing Hormone Antagonist on Gonadotropin-ll and Growth Hormone Release in Goldfish, <i>Carassius auratus</i>

Gonadotrophs but not somatotrophs carry gonadotrophin-releasing hormone receptors: receptor localisation, intracellular calcium, and gonadotrophin and GH release

Receptor Binding of Gonadotropin-Releasing Hormone Antagonists That Inhibit Release Of Gonadotropin-ll and Growth Hormone in Goldfish, Carassius Auratus1

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