Prolonged secretion of prolactin in response to thyrotrophin-releasing hormone after hypothalamo-pituitary disconnection in the ewe

Thomas, Graham H.; Cummins, J. T.; Hammond, James M.; Horton, R. J. E.; Clarke, I. J.

doi:10.1677/joe.0.1110433

Cited by 51 publications

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“…The tests that have been used are those that have been applied in both adult [49] and fetal [17,18,24] prepara tions.…”

Section: Functional Aspectsmentioning

confidence: 99%

“…The small residual response that was observed in the presence of a dopaminergic antagonist has also been ob served after stalk section in the fetal sheep [17] and was attri buted to the inhibition of extrahypothalamic dopamine. However, it is possible that chlorpromazine may stimulate the release of some as yet unidentified prolactin releasing factors [50], Although TRF is primarily a releasing hormone for thyroid-stimulating hormone, it has an intense stimulatory ef fect on pituitary lactotrophs in both adult [49] and fetal [1,6,17,23] sheep. In the present experiments there was no signifi cant difference in the prolactin response to TRF at 132-135 days in HPD fetuses when compared to sham-operated fe tuses, indicating that the functional activity of the anterior lobe, represented by the lactotroph, was not altered following HPD.…”

Section: Functional Aspectsmentioning

confidence: 99%

“…A prolonged response to TRF has been described in the fetal sheep [1,6,23] and in the adult ewe following HPD [49], suggesting that prolactin exerts a short-loop feedback on its own secre tion at the level of the hypothalamus in the adult ewe [49]. Our results indicate that there is a lack of negative feedback of prolactin on its own secretion in the fetal sheep in late gestation, although it is not clear whether this is due to a lack of prolactin receptors on the fetal hypothalamic do paminergic neurons or to an immaturity in other hypotha lamic neuronal pathways [51].…”

Section: Functional Aspectsmentioning

confidence: 99%

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Hypothalamo-Pituitary Disconnection in the Fetal Sheep

Clarke²,

et al. 1990

Neuroendocrinology

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In this study we have applied the technique of hypothalamo-pituitary disconnection (HPD) to the fetal sheep at 108–112 days of gestation. The pituitary is surgically disconnected from the hypothalamus by the removal of the neural component of the median eminence above the level of the portal circulation. This procedure results in the complete disconnection of the pituitary from the hypothalamus. After HPD, the lactotroph response to the dopamine antagonist chlorpromazine was significantly reduced (p < 0.005) indicating the functional isolation of the pituitary gland from the hypothalamus. The increase in plasma prolactin in response to exogenous thyrotrophin-releasing factor was maintained following HPD. HPD resulted in the complete atrophy of the pars nervosa. At 132–135 days of gestation after HPD there was no change in the volume or appearance of the pars distalis; small infarcts were observed in the pars distalis of some HPD fetuses, but these occupied less than 1% of the volume of the anterior lobe of the pituitary. There was a significant increase (p < 0.05) in the volume of the pars intermedia after HPD. Gestation was prolonged for at least 8 days beyond normal term following HPD, indicating that the processes integral to the initiation of parturition at term had been disrupted. We conclude that HPD provides a good in vivo model for the investigation of the activity of the isolated pituitary gland, and for the examination of the role of neuroendocrine mechanisms in fetal sheep development in the latter third of gestation.

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“…The tests that have been used are those that have been applied in both adult [49] and fetal [17,18,24] prepara tions.…”

Section: Functional Aspectsmentioning

confidence: 99%

Section: Functional Aspectsmentioning

confidence: 99%

Section: Functional Aspectsmentioning

confidence: 99%

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Hypothalamo-Pituitary Disconnection in the Fetal Sheep

Clarke²,

et al. 1990

Neuroendocrinology

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“…The efficacy of the HPD procedure was verified by challenging the ewes with 50 mg i.v. chlorpromazine (May and Baker Australia, Melbourne) and obtaining no prolactin response [29]. In the eighth experiment, mature lactating Romney ewes with free access to their lambs were used 25 30 days post partum.…”

Section: Animalsmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Associated Peptide (GAP) and Putative Processed GAP Peptides Do Not Release Luteinizing Hormone or Follicle-Stimulating Hormone or Inhibit Prolactin Secretion in the Sheep

Thomas

Cummins²,

Doughton³

et al. 1988

Neuroendocrinology

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A series of experiments was performed to monitor plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin responses to human gonadotropin-releasing hormone (GnRH) associated peptide (GAP) and related peptides. Ovariectomized hypothalamo-pituitary disconnected (HPD)ewes were challenged with injections (1–10 µg i.v.) of GAP, or given, with and without estradiol, hourly 500- or 1,000-ng pulses of GAP for 5–7 days. In all cases GAP failed to cause the release of LH or FSH from the pituitary gland or to alter mean plasma prolactin concentrations. When the same HPD ewes were given hourly or 2-hourly pulses of 250 ng GnRH, LH responded in a pulsatile manner, and FSH secretion was maintained, thus confirming the functional integrity of the pituitary gland after HPD. Fragments of the GAP molecule (pro-GnRH 14–36, 28–36, 38–49, and 51–66) and GAP dimer did not stimulate LH or FSH or inhibit prolactin release in HPD ewes. GAP and GAP dimer did not affect pituitary responsiveness to GnRH administration. GAP also failed to inhibit the thyrotropin-releasing hormone-induced rise in prolactin. Finally, GAP injections (100 µg i.v.) given to lactating ewes did not cause any change in plasma prolactin concentrations. These data show that human GAP, GAP dimer, or putative processed GAP peptides do not act on the sheep pituitary gland in a variety of physiological states to regulate gonadotropin or prolactin secretion.

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“…All the experiments were performed in 4 animals which had undergone the HPD operation 6 months previously, and the completeness of the procedure was confirmed biochemically by demonstrating an absent prolactin re sponse to chlorpromazine [52].…”

Section: Hypothalamic-pituitary Disconnectionmentioning

confidence: 99%

Studies of the Regulation of the Hypothalamic-Pituitary-Adrenal Axis in Sheep with Hypothalamic-Pituitary Disconnection. I. Effect of an Audiovisual Stimulus and Insulin-Induced Hypoglycemia

et al. 1988

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These studies were undertaken to characterize the secretion of adrenocorticotropin (ACTH), immunoreactive (ir) β-endorphin (ir-β-EP) and ir α-melanocyte-stimulating hormone (ir-α-MSH) from the surgically isolated ovine pituitary in response to an audiovisual stress (barking dog, 3 min) and insulin hypoglycemia. The studies were performed in 4 ovariectomized, hypothalamo-pituitary-disconnected (HPD) and 4 sham-HPD ewes bearing indwelling jugular venous catheters. Basal concentrations of the three pro-opiomelanocortin (POMC) peptides and plasma cortisol were significantly increased in the HPD animals. When the control ewes were exposed to the audiovisual stimulus, plasma ACTH, ir-β-EP and ir-α-MSH levels were increased 2.5-, 10-, and 5-fold 1 min after the stress; plasma cortisol attained maximal values at 5 min. In contrast, plasma levels of the three POMC peptides were not significantly increased in the HPD animals, although a rise in plasma cortisol occurred. The administration of regular insulin (5 units/kg i.v.) to control ewes caused plasma ACTH, ir-β-EP, and ir-α-MSH levels to increase 17-, 22-, and 67-fold at 50 min; plasma cortisol values were maximal at 60 min. In contrast, the elevated basal levels of POMC peptides in the HPD animals were not significantly increased by the hypoglycemia, but a significant elevation of plasma cortisol was seen. We conclude that: (1) the increase in ACTH in intact animals after an audiovisual emotional stress and hypoglycemia, and the abolition of this increase by HPD, indicates that both stimuli, each acting through distinct neuroanatomical pathways, increase the net corticotropin-releasing activity of the hypothalamus; (2) the rise in plasma cortisol in HPD animals after stress suggests that peripheral humoral factors may release additional small amounts of ACTH from the anterior pituitary, and (3) the finding of increased basal ACTH levels after HPD suggests that POMC peptide synthesis and secretion by the anterior pituitary is tonically regulated by an inhibitory factor of hypothalamic origin.

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Prolonged secretion of prolactin in response to thyrotrophin-releasing hormone after hypothalamo-pituitary disconnection in the ewe

Cited by 51 publications

References 0 publications

Hypothalamo-Pituitary Disconnection in the Fetal Sheep

Hypothalamo-Pituitary Disconnection in the Fetal Sheep

Gonadotropin-Releasing Hormone Associated Peptide (GAP) and Putative Processed GAP Peptides Do Not Release Luteinizing Hormone or Follicle-Stimulating Hormone or Inhibit Prolactin Secretion in the Sheep

Studies of the Regulation of the Hypothalamic-Pituitary-Adrenal Axis in Sheep with Hypothalamic-Pituitary Disconnection. I. Effect of an Audiovisual Stimulus and Insulin-Induced Hypoglycemia

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