Refractoriness of the Pituitary Gland After Continuous Exposure to Luteinizing Hormone Releasing Hormone

Koning, J. de; Dieten, J. A. M. J. van; Rees, G. P. van

doi:10.1677/joe.0.0790311

Cited by 94 publications

(25 citation statements)

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“…Preliminary data do indicate that the de sensitization observed after continuous exposure of some hours duration is caused by a different mechanism: when acutely desensitized pituitary glands were incubated with supra-maximally active concentrations of LH-RH. LH re lease was not diminished, as opposed to LH release after continuous exposure to LH-RH for several hours [10].…”

Section: Methodsmentioning

confidence: 70%

Short-Term Pituitary Desensitization to LH-RH after Pulsatile LH-RH in the Ovariectomized Rat: An in vivo Experiment

et al. 1986

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The development of acute insensitivity of pituitary LH secretion to LH-RH after a short exposure to LH-RH is described. In the first experiment, ovariectomized (OVX), phenobarbital-pretreated rats were given pulses of LH-RH (1.25 or 6.25 ng/100 g body weight (b.w.), intravenously). In rats given 1.25 ng at time 0,6.25 ng at 60 min, 1.25 ng at 80 min and 1.25 ng at 120 min, there was a substantial increase in plasma LH after the first two injections, no increase after the third injection and a relatively small increase after the fourth one. In other rats treated identically but not given a 1.25-ng dose at 80 min, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after the 1.25-ng dose given at time 0. If the 1.25-ng LH-RH pulses given at times 0 and 80 min were replaced by a rat pituitary extract, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after administration of pituitary extract. In the second experiment, OVX phenobarbital-pretreated rats were given 1.25 ng LH-RH/100 gb.w. at t = 0. They were then divided into three groups, each receiving 1.25, 3.75 or 6.25 ng LH-RH/100 g b.w. at t = 60 min. Each of these three groups was again divided into three groups which received 1.25 ng LH-RH/100 g b.w. at 80, 100 or 120 min. The response to 1.25 ng LH-RH/100 g b.w. was significantly depressed at t = 80 min in the animals that had received a dose of 3.75 or 6.25 ng LH-RH/100 gb.w. at t = 60 min. At t= 100 min a significantly decreased response was still observed in the animals which had been treated with a dose of 6.25 ng LH-RH/100 g b.w. at t = 60 min. It is concluded that, in the OVX rat, a single dose of LH-RH can induce short-term desensitization of pituitary gland LH release in response to LH-RH. The duration of this short-term desensitization is related to the dose of LH-RH that causes it. This desensitization may have physiological significance in establishing pulsatile rhythms of LH release.

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Section: Methodsmentioning

confidence: 70%

Short-Term Pituitary Desensitization to LH-RH after Pulsatile LH-RH in the Ovariectomized Rat: An in vivo Experiment

et al. 1986

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“…Thus, TX seemed to act as an estrogen agonist on GnRH self-priming and as an estrogen antagonist on GnRH-stimulated LH secretion. During continuous exposure of pituitary glands to GnRH the phenomenon of pituitary desensitization to GnRH cannot be overlooked [17, 31]. The GnRH self-priming effect is better recognized if the interval between two consecutive GnRH pulses, the physiological manner in which GnRH is released [32], is separated by 60 min [1].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the triphenylethylene tamoxifen (TX) increases LH accumulation in a 4-hour incubation of proestrous pituitary in the same way as estrogen [16]. Without disregarding the possible phenomenon of pituitary desensitization under continuous exposure to GnRH [17], accumulated LH in incubation medium during prolonged exposure to GnRH may be the result of a complex secretory process involving basal, GnRH-stimulated LH secretion and GnRH self-priming.…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen but Not Other Selective Estrogen Receptor Modulators Antagonizes Estrogen Actions on Luteinizing Hormone Secretion while Inducing Gonadotropin-Releasing Hormone Self-Priming in the Rat

Sánchez-Criado

Guelmes²,

Bellido

et al. 2002

Neuroendocrinology

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Selective estrogen receptor modulators (SERMs) are compounds which may function as agonists or antagonists depending upon the target tissue. This study compares the actions of different SERMs on luteinizing hormone (LH) secretion, and on gonadotropin-releasing hormone (GnRH) self-priming in the rat. To do this, 4-day cyclic rats were injected twice, on day 2 (metestrus) and day 3 of the estrous cycle, with one of the following SERMs: 0.25 mg ICI 182,780, 3 mg tamoxifen (TX), LY139481-HCl or LY117018-HCl, or 0.5 mg RU58668. Control rats were given subcutaneous injections of 0.2 ml oil. On the morning of day 4 (proestrus in controls), rats from each group were either injected intraperitoneally with pentobarbital (40 mg/kg) for in vivo study or decapitated and their pituitaries collected for incubation (in vitro study). Additionally, pituitaries taken on each day of the estrous cycle from control rats as well as on day 4 from SERM-treated rats were processed for immunohistochemical determination of the estrogen receptor-α (ERα) gonadotrope. The plasma concentration or accumulation of LH in the medium was determined after 1 h (basal secretion). Thereafter, an intravenous bolus of GnRH (50 ng/0.5 ml/100 g BW) or 10^–8M GnRH was injected or added to the medium, respectively. After 1 h of GnRH exposure, blood or medium were taken, and another challenge of GnRH was made. At the end of the 3rd h of the experiment, blood or medium samples were taken again and the LH plasma concentration or accumulation in the medium were determined. All SERM treatments reduced uterus weight and decreased basal and stimulated LH secretion. Also, on day 4, rats treated with any SERM other than TX showed vaginal smears infiltrated by leukocytes and a reduction in GnRH self-priming. TX-treated rats exhibited cornified vaginal smears and an estrogenic effect on GnRH self-priming. Moreover, 15-min exposure to two consecutive GnRH (10^–8M) challenges 1 h apart in incubated pituitaries with estradiol (E₂, 10^–8M), TX (10^–7M), E₂ + TX, or medium alone form ovariectomized rats injected for 3 days with estradiol benzoate (25 µg), TX (3 mg), estradiol benzoate + TX, or 0.2 ml oil, respectively, showed that TX increased GnRH self-priming, as did E₂, whereas it reduced the E₂-sensitizing effect on GnRH-stimulated LH secretion and cancelled the E₂-dependent GnRH self-priming. All SERMs prevented the physiological nucleocytoplasmic shuttling of ERα exhibited during proestrus in control rats, and TX, in addition, induced a significantly larger number of gonadotropes displaying strong cytosolic immunosignals corresponding to ERα than the rest of the experimental groups. Overall, data from this study indicated that, in contrast to the general antagonistic effect of the tested SERMs, TX seemed to display both selective agonist and antagonist activity at the gonadotrope level and on GnRH self-priming of LH secretion respectively.

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“…This stimulation pattern maintains responsiveness to GnRH, whereas continuous stimulation causes desensitization and attenuates gonadotropin secretion (16,38). Recent studies (24) ]inositol and stimulated in the presence of LiCl) remains linear for 10 min after stimulation.…”

Section: Discussionmentioning

confidence: 99%

Desensitization of Gonadotropin-releasing Hormone Action in αT3-1 Cells Due to Uncoupling of Inositol 1,4,5-Trisphosphate Generation and Ca2+ Mobilization

McArdle

Willars

Fowkes

et al. 1996

Journal of Biological Chemistry

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Gonadotropin-releasing hormone (GnRH) acts via a G-protein coupled receptor on gonadotropes to increase cytosolic Ca 2؉ and stimulate gonadotropin secretion. Sustained exposure causes desensitization of these effects, but the GnRH receptor has no C-terminal tail and does not undergo rapid (<5 min) desensitization. Nevertheless, pretreatment of ␣T3-1 cells with GnRH reduced the spike Ca 2؉ response to GnRH and decreased the GnRH effect on inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3 ) by 30 -50%. Ca 2؉ -free medium with or without thapsigargin also decreased GnRH-stimulated Ins(1,4,5)P 3 generation, implying that attenuation of the Ca 2؉ response underlies the Ins(1,4,5)P 3 reduction rather than vice versa. Intracellular Ca 2؉ pool depletion cannot explain desensitization of the Ca 2؉ response because pool depletion and repletion were faster (half-times, <1 min) than the onset of and recovery from desensitization (halftimes 10 -20 min and 4 -6 h). Moreover, 1-h GnRH pretreatment attenuated the spike Ca 2؉ response to GnRH but not that to ionomycin, and brief GnRH exposure in Ca 2؉ -free medium reduced the response to ionomycin more effectively in controls than in desensitized cells. GnRH pretreatment also attenuated the Ca 2؉ response to PACAP38. This novel form of desensitization does not reflect uncoupling of GnRH receptors from their immediate effector system but rather a reduced efficiency of mobilization by Ins(1,4,5)P 3 of Ca 2؉ from an intact intracellular pool.

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Refractoriness of the Pituitary Gland After Continuous Exposure to Luteinizing Hormone Releasing Hormone

Cited by 94 publications

References 0 publications

Short-Term Pituitary Desensitization to LH-RH after Pulsatile LH-RH in the Ovariectomized Rat: An in vivo Experiment

Short-Term Pituitary Desensitization to LH-RH after Pulsatile LH-RH in the Ovariectomized Rat: An in vivo Experiment

Tamoxifen but Not Other Selective Estrogen Receptor Modulators Antagonizes Estrogen Actions on Luteinizing Hormone Secretion while Inducing Gonadotropin-Releasing Hormone Self-Priming in the Rat

Desensitization of Gonadotropin-releasing Hormone Action in αT3-1 Cells Due to Uncoupling of Inositol 1,4,5-Trisphosphate Generation and Ca2+ Mobilization

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