INHIBITORY ACTIVITY OF ANALOGUES OF LUTEINIZING HORMONE‐RELEASING HORMONE (LH‐RH) <i>IN VITRO</i> AND <i>IN VIVO</i>

Ferland, Louise; Labrie, Fernand; Savary, Muriel; Beaulieu, Martin; Coy, David H.; Coy, Esther J.

doi:10.1111/j.1365-2265.1976.tb03836.x

Cited by 13 publications

(8 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Measurement of Biological Activity and Calculations. The agonistic and antagonistic activities of the LH-RH analogs were measured as the potency of the peptides to stimulate and inhibit, respectively, the LH-RH-induced LH release in rat anterior pituitary cells in primary culture (23)(24)(25). Kd values for LHreleasing activity were determined as the peptide ED5o for LH release.…”

mentioning

confidence: 99%

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

Reeves¹,

Séguin²,

Lefebvre³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

To study the luteinizing hormone-releasing hormone (LH-RH; luliberin) (7)(8)(9)(10)(11)(12). Because the antifertility effects of LH-RH and its analogs are parallel to their gonadotropin-releasing potency, the loss of ovarian gonadotropin receptors and inhibition of steroidogenesis could be due at least partly to endogenous luteinizing hormone (LH) release (5, 11, 13). However, direct ovarian effects of LH-RH agonists have been observed in female rats (14-17). LH-RH agonists have also been found to inhibit steroid secretion stimulated by human choriogonadotropin or follicle-stimulating hormone in rat luteal and granulosa cells (17-19 500 ,uCi (1 Ci = 3.7 X 1010 becquerels) of carrier-free Nal25I, and 600 ng of chloramine-T in 10,Ml of 0.5 M sodium phosphate (pH 7.2). The reaction was stopped by adding 1 ml of eluant buffer (10 mM Tris-HCI/0.1% bovine serum albumin/0.1% NaN3, pH 7.6 at 250C) and immediately layering onto a 1 X 55 cm column of Sephadex G-25 (fine). This procedure has been shown to separate monoiodinated and diiodinated hormones (20). Free 125I eluted as the first radioactive peak; monoiodinated [D-Ser(TBU)6]-LH-RH-EA appeared as the second radioactive peak. As of maximal effect.

show abstract

mentioning

confidence: 99%

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

Reeves¹,

Séguin²,

Lefebvre³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

show abstract

“…It is well known from previous investigations on the pharmacology of narcotics that narcotic drugs affect the secretion of several pituitary hormones, including prolactin, growth hormone, vasopressin, and adrenocorticotropic hormone (ACTH). Morphine is a potent releaser of prolactin, growth hormone, and vasopressin (1)(2)(3)(4). Recently, it has been shown that enkephalin analogs can also increase blood prolactin levels (5).…”

mentioning

confidence: 99%

Morphine and endorphins modulate dopamine turnover in rat median eminence.

Deyo¹,

Swift²,

Miller³

1979

Proc. Natl. Acad. Sci. U.S.A.

134

View full text Add to dashboard Cite

There is evidence that some of the actions of both endogenous and exogenous opioids (e.g., stimulation of prolactin release) are mediated by interaction with catecholaminergic systems. Morphine (1.67, 5, and 15 mg/kg of body weight, intraperitoneally) altered dopamine turnover as measured by the a-methyl-p-tyrosine method in the median eminence, neostriatum, and frontal cortex of male Sprague-Dawley rats. The turnover rate of dopamine was reduced in the median eminence and frontal cortexbut accelerated in the neostriatum. In the frontal cortex all doses were effective in decreasing dopamine turnover; however, in the median eminence the lowest dose of morphine did not significantly alter dopamine turnover. All three doses accelerated dopamine turnover in the neostriatum. Naloxone effectively reversed the effects of morphine at all doses in all brain areas, whereas it had no effect on turnover when given alone. In the median eminence, neostriatum, and frontal cortex, intraventricular injection of D-Ala2,D-Leu5J enkephalin (25 Mug) or fl-endorphin (15 ,g) produced the same effects on dopamine turnover as morphine. The actions of these peptides were blocked by naloxone. It is hypothesized that opiates and opioid peptides increase prolactin release by reducing the activity of the tuberoinfundibular dopaminergic system.Since the discovery of the endorphins and the enkephalins, peptides with opiate agonist activity, intensive investigations have been carried out in order to define the functions of these peptides in the nervous system. It is becoming evident that one such important role may be in the control of the release of hormones from the pituitary gland. It is well known from previous investigations on the pharmacology of narcotics that narcotic drugs affect the secretion of several pituitary hormones, including prolactin, growth hormone, vasopressin, and adrenocorticotropic hormone (ACTH). Morphine is a potent releaser of prolactin, growth hormone, and vasopressin (1-4). Recently, it has been shown that enkephalin analogs can also increase blood prolactin levels (5).Immunohistochemical studies on enkephalin distribution within the brain have defined several potential enkephalinergic pathways that may serve to regulate the release of these hormones (6). Thus, an enkephalin-containing neuronal system projecting from the paraventricular nucleus of the hypothalamus to the pars nervosa of the pituitary may serve to regulate the release of vasopressin (7). In addition, it has been shown that the median eminence contains a large number of enkephalinergic nerve endings (6). Because it is known that endorphins and morphine do not produce their releasing actions on pituitary prolactin by direct action on pituitary lactotrophs (8, 9), it therefore appears that this action of these opioid compounds is mediated at the level of the hypothalamus.Because the main hypothalamic control of prolactin secretion is mediated by hypothalamic dopaminergic neurons (10), we investigated the possibility that the releasing effects of...

show abstract

“…These agonist properties were only weakly present; the potency of the compound was estimated to be less than 1% of that of native bPTH-(1-84) on a molar basis [3]. Similar difficulties have been encountered in other hormone systems when antagonists that were potent in vitro were brought to evaluation in vivo [24][25][26][27][28]. The reasons for the discrepancy between agonist and antagonist responses in vitro and in vivo remain to be elucidated.…”

Section: Discussionmentioning

confidence: 83%

Analogues of an in vitro parathyroid hormone inhibitor: Modifications at the amino terminus

Rosenblatt

Potts

1981

Calcif Tissue Int

View full text Add to dashboard Cite

Four analogues of parathyroid hormone were synthesized, based on a sequence previously shown to yield an in vitro inhibitor of PTH action. Binding properties of the analogues to presumed parathyroid hormone receptors were evaluated. Each of these analogues contains a structural alteration of the amino terminus of the compound [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide. Each of the analogues--[desamino-Ser-3, Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide, [acetyl-Glu-4, Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide, [D-Ser-3, Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide, and [pyroGlu-4, Nle-8, Nle-18, Tyr-34]bPTH-3(3-34)amide--contains modifications selected to diminish or eliminate the weak PTH-like agonist properties detected in the parent compound in vivo. To permit valid comparison of receptor-binding properties, all the analogues were derived from a common solid-phase synthesis. When assayed in the renal adenylate cyclase assay, each of the compounds inhibited completely PTH-stimulated adenylate cyclase activity and was devoid of PTH-like agonist activity. To compare the binding affinity of the analogues for parathyroid hormone binding sites, the peptides were evaluated in a parathyroid hormone renal radioreceptor assay. Each peptide demonstrated a binding affinity comparable with one another and only slightly weaker than that of the unmodified inhibitory analogue, [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide. These studies demonstrate that it is possible to alter the amino terminus of parathyroid hormone analogues without causing a dramatic decline in affinity for the parathyroid hormone receptor. Preservation of high receptor-binding affinity in these analogues indicates that synthesis of one or several of these peptides on a scale sufficiently large to permit in vivo evaluation of both agonist and antagonist properties is warranted.

show abstract

INHIBITORY ACTIVITY OF ANALOGUES OF LUTEINIZING HORMONE‐RELEASING HORMONE (LH‐RH) IN VITRO AND IN VIVO

Cited by 13 publications

References 15 publications

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

Morphine and endorphins modulate dopamine turnover in rat median eminence.

Analogues of an in vitro parathyroid hormone inhibitor: Modifications at the amino terminus

Contact Info

Product

Resources

About