A new method for studying pituitary responsiveness in vivo using pulses of LH-RH analogue in ewes passively immunized against native LH-RH

Caraty, Alain; Martin, G.B.; Montgomery, G. W.

doi:10.1051/rnd:19840409

Cited by 19 publications

(6 citation statements)

References 17 publications

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“…2 Pulsatile LH secretion from the pituitary is itself driven by intermittent secretion of gonadotropin-releasing hormone (GnRH) from the brain. 3,4 However, hot flashes are clearly not dependent on pulsatile LH itself since they occur even in its absence. 5 Rather, it seems the same upstream afferent input responsible for driving GnRH neurons is responsible for triggering hot flashes.…”

Section: Introductionmentioning

confidence: 99%

κ Agonists as a novel therapy for menopausal hot flashes

et al. 2015

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Objective Postmenopausal hot flash etiology is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing Kisspeptin, Neurokinin B, and Dynorphin (KNDy neurons), located adjacent to the thermoregulatory center, regulate pulsatile secretion of GnRH and LH. Dynorphin may inhibit this system by binding kappa opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. Methods A double-blind, cross-over, placebo-controlled pilot study evaluated the effect of a kappa agonist (KA).Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate-severe hot flashes, ages 48-60 years, were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all 3 interventions: placebo, standard Pentazocine/Naloxone (50/0.5 mg) or low-dose Pentazocine/Naloxone (25/0.25 mg). In an inpatient research setting, each participant received the 3 interventions, in randomized order, on 3 separate days. On each day, an intravenous catheter was inserted for luteinizing hormone (LH) blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. Results Mean hot flash frequency 2-7 hours following therapy initiation was lower than that for placebo (KA standard-dose: 4.75 ± 0.67; KA low-dose: 4.50 ± 0.57; and placebo: 5.94 ± 0.78 hot flashes/5 hours; p =0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some, but not all women. Conclusions This pilot suggests that kappa agonists may affect menopausal vasomotor symptoms.

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Section: Introductionmentioning

confidence: 99%

κ Agonists as a novel therapy for menopausal hot flashes

et al. 2015

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“…This concept of an LHRH pulse generator was the result of many indirect and some direct demon¬ strations of the relationship between LHRH and LH secretion. Antibodies to LHRH will block LH pulses in the ram and ewe (Lincoln & Fraser, 1979;Caraty et ai, 1984) and the pulsatile pattern of LH secretion can be restored by pulsatile delivery of an LHRH agonist (Caraty et al, 1984;Adams & Adams, 1986). Most conclusive is the demonstration in the hypophysial portal blood of ewes that LHRH is secreted in a pulsatile manner (Caraty et al, 1982;Clarke & Cummins, 1982).…”

Section: Introductionmentioning

confidence: 99%

Effect of time after castration on secretion of LHRH and LH in the ram

Caraty¹,

Locatelli²

1988

Reproduction

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167

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Summary. Hypophysial portal blood and peripheral blood were obtained from conscious, unrestrained rams to measure simultaneously the secretion of LHRH and LH in entire rams and rams which had been castrated for 2\p=n-\15 days (short-term castration) and for 1\p=n-\6months (long-term castration). The apparatus for portal blood collection was surgically implanted using a transnasal trans-sphenoidal approach and, 4\p=n-\5 days later, portal blood and peripheral blood were collected simultaneously at 10-min intervals for 8\p=n-\9h from 15 sheep. LHRH was clearly secreted in pulses in all three physiological conditions, but there were marked differences in pulse frequencies, which averaged 1 pulse/2\p=n-\4 h in entire rams, 1 pulse/70 min in short-term castrated rams and 1 pulse/36 min in long-term castrated rams. In entire and short-term castrated animals, LH profiles were also clearly pulsatile and each LHRH pulse in hypophysial portal blood was associated with an LH pulse in the peripheral blood. In long-term castrated animals, LH pulses were not as well defined, because of the high basal levels and small pulse amplitudes, and the temporal relationship between LHRH and LH pulses was not always clear. These results demonstrate the pulsatile nature of LHRH secretion under the three physiological conditions and suggest that the irregular LH profiles characteristic of long-term castrates are due to an inability of the pituitary gland to transduce accurately the hypothalamic signal. The very high frequency of the LHRH pulses may be one of the major reasons for this, and is probably also responsible for the high rate of LH secretion in the long-term castrated animal.

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“…However, during the breeding season pretreatment concentrations of LH are restored 12 to 24 h after beginning E 2 infusion in wethers receiving concurrent episodic GnRH stimulation (Sakurai & Adams 1991, Sakurai et al 1996. A similar biphasic pattern of LH secretion is noted in E 2 -treated ovariectomized sheep made deficient in endogenous GnRH by hypothalamic-pituitary disconnection (Clarke & Cummins 1984, Clarke et al 1988 or passive immunization (Caraty et al 1984, Herman & Adams 1990) and receiving hourly pulses of GnRH or a GnRH agonist. Biphasic effects of E 2 on gonadotrope responsiveness are also evident in vitro (Frawley & Neill 1984, Ortmann et al 1988.…”

Section: Discussionmentioning

confidence: 57%

The effect of season and melatonin on GnRH-induced LH secretion in oestradiol-treated orchidectomized sheep

Sakurai

Adams²

1998

Journal of Endocrinology

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The biphasic effect of oestradiol (E 2 ) on gonadotrope responsiveness is clearly evident in orchidectomized sheep (wethers) receiving E 2 and hourly pulses of GnRH. We hypothesized that the duration of E 2 -induced reduction in gonadotrope responsiveness differed between the breeding (November) and anoestrous (May) seasons in sheep. To test this hypothesis wethers (n=6/group) were infused (i.v.) with E 2 (2 µg/50 kg per h) and received hourly pulses of GnRH (200 ng/50 kg per pulse) or saline in May or November. The pattern of LH secretion during the 72 h infusion period was determined. Serum concentrations of LH did not differ with season in control wethers receiving vehicle alone. Similarly, continuous infusion of E 2 resulted in a 3-fold reduction in serum LH, irrespective of season. This E 2 -induced suppression of serum LH was reversed by concurrent episodic delivery of GnRH. The interval between initiation of infusion and return of pretreatment concentrations of LH was taken as a measure of the duration of E 2 -induced suppression of gonadotrope responsiveness. The duration of this E 2 -dependent response varied with season, with suppression of gonadotrope responsiveness more prolonged (P<0·05) in May (36·7 2·9 h) than in November (14·3 1·1 h). In a companion study we examined the effect of melatonin on the duration of E 2 -induced suppression of gonadotrope responsiveness. Wethers received blank or melatonincontaining implants in March. Sixty days after implant insertion (mid-May) wethers received E 2 (2 µg/50 kg per h) and hourly pulses of GnRH (200 ng/50 kg per pulse) or saline for 72 h. Continuous delivery of E 2 alone resulted in a 3-fold decrease in serum concentrations of LH in both control and melatonin-treated wethers. The duration of E 2 -induced suppression of gonadotrope responsiveness in animals receiving E 2 and GnRH was extended (P<0·05) in wethers with blank implants (48·0 0·7 h), relative to the duration of suppression in melatonin-treated wethers (14·5 1·0 h). Taken together these data indicate that E 2 -induced suppression of gonadotrope responsiveness is more extended during the anoestrous season. However, this seasonal effect can be reversed by continuous administration of melatonin.

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A new method for studying pituitary responsiveness in vivo using pulses of LH-RH analogue in ewes passively immunized against native LH-RH

Abstract: Introduction.

Cited by 19 publications

References 17 publications

κ Agonists as a novel therapy for menopausal hot flashes

κ Agonists as a novel therapy for menopausal hot flashes

Effect of time after castration on secretion of LHRH and LH in the ram

The effect of season and melatonin on GnRH-induced LH secretion in oestradiol-treated orchidectomized sheep

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