Elevated serum DHEA-S levels in association with hyperprolactinemia

Serum DHEA-S levels were significantly higher in women with hyperprolactinemia than in normal women during the early follicular phase. When comparison was made of serum DHEA-S levels in hyper-and normoprolactinemic patients with secondary amenorrhea due to hypothalamic-pituitary failure, serum DHEA-S levels were significantly higher in hyperprolactinemic patients than in normoprolactinemic patients. This indicates elevated serum DHEA-S levels in association with hyperprolactinemia, but not with amenorrhea pe se.     

Prolactin secretion in patients with idiopathic diabetes insipidus.

It has been demonstrated that hyperprolactinemia is sometimes present even in patients with idiopathic diabetes insipidus (DI). In this study, we examined the responses of serum prolactin (PRL) to hypertonic saline infusion and TRH injection in 11 patients with idiopathic DI diagnosed by clinical examinations. Serum sodium in these patients (147.5 +/- 3.2 mEq/L) was significantly higher at baseline than in normal subjects (139.7 +/- 2.4 mEq/L). The plasma arginine vasopressin (AVP) level was significantly lower in DI (0.42 +/- 0.24 pg/ml) at baseline than in normal subjects (2.53 +/- 1.03 pg/ml). However, the serum PRL level in both groups did not differ significantly except in one patient with idiopathic DI (35.6 ng/ml). There was no significant correlation between the basal serum sodium and basal serum PRL in either group. After an infusion of hypertonic saline, the serum sodium level gradually increased to 155.6 +/- 3.4 mEq/L in DI and to 146.5 +/- 4.3 mEq/L in the normal subjects. However, this increase did not affect PRL secretion in either group. PRL response to TRH was essentially normal in all patients with idiopathic DI. These results indicate that the secretion of PRL is not generally affected by chronic mild hypernatremic hypovolemia in the patients with idiopathic DI.     

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.     

Estrogen feedback in normal and sulpiride-induced hyperprolactinemic postmenopausal women

Feedback effect of estrogen on gonadotropin secretion was studied in normal and sulpiride-induced hyperprolactinemic postmenopausal women. Twelve normoprolactinemic postmenopausal women were administered 40 micrograms/day of ethinyl estradiol (EE2) orally throughout the study. On the 4th week of the study, daily doses of 200 micrograms EE2 were also given to each subject for 4 days. Twelve postmenopausal women were given sulpiride orally in a daily dose of 150 mg throughout the study. Serum levels of prolactin were raised in all 12 subjects given sulpiride. In the 12 sulpiride-induced hyperprolactinemic postmenopausal women, EE2 was given in the same manner as in normal postmenopausal women. The negative feedback effect of estrogen with low doses of EE2 (40 micrograms/day for 4 weeks) and the positive feedback effect of estrogen after the subsequent administration of EE2 (200 micrograms/day for 4 days) were demonstrated in both normoprolactinemic and hyperprolactinemic groups. The result of the present study suggests that sulpiride-induced hyperprolactinemia does not affect the negative and positive feedback effect of estrogen in postmenopausal women.     

Catecholamines and pituitary function. III. Restoration of the prolactin response to thyrotropin-releasing hormone by low-dose dopamine infusion in women with pathological hyperprolactinemia

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.     

Effects of indomethacin on postural hypotension in Parkinsonism.

A study was conducted to evaluate the effect of indomethacin on orthostatic hypotension in Parkinsonism. Twelve elderly patients participated and the drug was given in two-ways--as an intravenous infusion of 50 mg over 30 minutes and by mouth 50 mg thrice daily for six days. Results were assessed by measuring the degree of hypotension on standing, response to the cold pressor test, and forearm blood flow (by strain-gauge plethysmography). Indomethacin significantly reduced the fall in blood pressure on standing (P less than 0:001) and lessened or reversed orthostatic symptoms. Furthermore, there was an enhanced response to the cold pressor test and a reduction in forearm blood flow. These findings suggest that indomethacin has a positive effect on systemic vascular resistance.     

Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300-325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg(-1)·h(-1)) or dextrose prior to a 60-min fixed-pressure hemorrhage (～40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg(-1)·min(-1)). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition.     

Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulatory galanin levels increase severalfold with intense orthostatic challenge in healthy humans.

The purpose of this study was to test the hypothesis that plasma galanin concentration (pGal) is regularly increased in healthy humans with extensive orthostatic stress. Twenty-six test persons (14 men, 12 women) were brought to an orthostatic end point via a progressive cardiovascular stress (PCS) protocol consisting of 70 degrees head-up tilt plus increasing levels of lower body negative pressure until either hemodynamically defined presyncope or other signs of orthostatic intolerance occurred (nausea, clammy skin, excessive sweating, pallor of the skin). We further tested for possible gender, gravitational, and muscular training influences on plasma pGal responses: PCS was applied before and after 3 wk of daily vertical acceleration exposure training on a Human Powered Centrifuge. Test persons were randomly assigned to active (with bicycle work) or passive (without work) groups (seven men, six women in each group). Resting pGal was 26+/-3 pg/ml in men and 39+/-15 pg/ml in women (not significant); women had higher galanin responses (4.9-fold increase) than men (3.5-fold, P=0.017) to PCS exposure. Overall, PCS increased pGal to 186+/-5 pg/ml (P=0.0003), without significant differences between presyncope vs. orthostatic intolerance, pre- vs. postcentrifuge, or active vs. passive gravitational training. Increases in pGal were poorly related to synchronous elevations in plasma vasopressin. We conclude that galanin is regularly increased in healthy humans under conditions of presyncopal orthostatic stress, the response being independent of gravity training but larger in women than in men.     

Sequence of pituitary-adrenal cortical hormone responses to low-dose physostigmine administration in young adult women and men

We previously demonstrated greater HPA axis activation in adult men compared to adult women following low-dose administration of the anticholinesterase inhibitor, physostigmine (PHYSO). Because blood sampling was done infrequently following PHYSO, the rise times of AVP, ACTH1-39, and cortisol could not be determined. In the present study, we determined the sequence of hormone increases by frequent blood sampling following PHYSO. Twelve adult women and 12 adult men underwent three test sessions 5-7 days apart: PHYSO, saline control, and repeat PHYSO. As in the earlier study, PHYSO produced no side effects in half the subjects and mild side effects in the other half, with no significant female-male differences. None of the hormone responses was significantly correlated with the presence or absence of side effects. In both women and men, the AVP increase preceded the ACTH1-39 increase, which in turn preceded the cortisol increase. The AVP and ACTH AUCs were significantly positively correlated in both women and men, supporting AVP as an acute stimulus to ACTH secretion. Also as in the earlier study, the AVP response to PHYSO was more than twice as great in men as in women, but the difference was not statistically significant. We therefore analyzed the results of both studies combined (N=26 women and 26 men). The men had a significantly greater AVP response and a trend toward a greater ACTH1-39 response compared to the women. These findings further support the concept of sexual diergism (functional sex difference) in the influence of CNS cholinergic systems on HPA hormone secretion.     

3H]AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin

The interaction of an antagonist of arginine vasopressin (AVP), d(CH2)5-D-Tyr(Et)VAVP, with renal tubular V2 receptors were studied in medullary membrane preparations from kidneys of Sprague-Dawley and Brattleboro rats. In both rat strains, V2 receptors had comparable KD and Bmax values for binding of [3H]AVP. In vitro studies revealed that the V2-antagonist was more potent than cold AVP in displacing [3H]AVP. In vivo treatment of Sprague-Dawley rats with the antagonist over one week resulted only in a transient state of diabetes insipidus (DI). No specific [3H]AVP binding was detectable throughout the period of administration. Chronic treatment of Brattleboro rats resulted in a complete normalization of water intake. This agonistic effect was also associated with undetectable [3H]AVP binding. After stopping the infusion of d(CH2)5-D-Tyr(Et)VAVP, Bmax values tended to rise but had still not reached base line values after 6 days. In contrast, the chronic infusion of AVP in Brattleboro rats resulted in a reduction in water intake which was accompanied by a decreased Bmax. [3H]AVP binding remained detectable during the entire treatment period. Thereafter Bmax was restored to base line values within 2 days of stopping the infusion. These results suggest that d(CH2)5-D-Tyr(Et)VAVP has a high affinity for V2 receptors in both Sprague-Dawley and Brattleboro rats. Its rate of dissociation from the receptor appears to be much slower than that of AVP. In Brattleboro rats, the binding of d(CH2)5-D-Tyr(Et)VAVP leads to an antidiuretic response. In Sprague-Dawley rats, a transient diuretic response is followed by a progressive normalization in water intake. This occurs despite persistent and complete blockade of renal medullary V2 receptors.     

Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.     

Mammalian FMRF-NH2-like peptide in rat pituitary: decrease by osmotic stimulus.

Previous studies with the Brattleboro rat suggested a possible interaction at the pituitary level between AVP and the neuropeptide, F-8-F-NH₂. In order to test this hypothesis, we studied the effect of various osmotic stimuli on neurohypophyseal F-8-F-NH₂. In rats drinking 2% NaCl solution for two days, neural lobe AVP and F-8-F-NH₂ levels were equally reduced by 87%. After maximal depletion, pituitary levels of F-8-F-NH₂ and AVP rebounded in parallel when normal drinking water was reintroduced. Pituitary stalk transection depleted neurohypophyseal F-8-F-NH₂. The results of this study suggest that neurohypophyseal F-8-F-NH₂ originates from the hypothalamus and, furthermore, is coreleased along with AVP in response to hyperosmotic stimuli.     

Arginine-vasopressin and oxytocin response to cholecystokinin-tetrapeptide.

This study examined the effects of i.v. administration of cholecystokinin-tetrapeptide (CCK-4) on plasma release of arginine vasopressin (AVP) and oxytocin (OT) in women with premenstrual dysphoric disorder (PMDD) and control women, during both the follicular phase and the luteal phase of their menstrual cycle. Plasma AVP and OT concentrations increased following CCK-4 administration. AVP and OT response to CCK-4 was similar for PMDD and control women and unaffected by menstrual cycle phase. AVP and OT may play a role in the hypothalamo-pituitary adrenal (HPA) axis activity associated with the panic response induced by CCK-4.     

Effects of arginine vasopressin on blood pressure and renal prostaglandin E2 in rabbits.

The role of arginine vasopressin (AVP) in blood pressure regulation in humans and animals is still controversial. The present study was designed to investigate the effects of AVP on blood pressure and the excretion of sodium and prostaglandin (PG) E2 in rabbits. AVP dissolved in 0.01 M acetic acid was infused subcutaneously at a rate of 0.86 ng/kg/min with a miniosmotic pump into 12 New Zealand white rabbits (2.7-3.4 kg), while 10 controls were given vehicle alone. AVP infusion resulted in a 3.5-fold rise in the level of plasma AVP (21.8 +/- 4.4 (SEM) pg/ml) as compared with controls, associated with a significant decrease in the urine volume and urinary excretion of sodium. The PGE2 excretion was increased 1.8-fold after AVP infusion. In the chronic AVP-infused group, blood pressure was not significantly increased, but the acute vascular response to AVP was significantly attenuated without any changes in the vasopressor response to angiotensin II. Preadministration of V1-antagonist completely abolished the vasopressor action of AVP, but not that of angiotensin II, in either group. These results suggest that circulating AVP within physiological range of concentrations may stimulate renal PGE2 synthesis and attenuate the vascular response through vascular V1 receptors without affecting the baroreflex, which may be attenuated through V2 receptors.     

Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.     

Prolactin suppresses GnRH but not TSH secretion

BACKGROUND/AIMS: In animal models, prolactin increases tuberoinfundibular dopamine turnover, which has been demonstrated to suppress both hypothalamic GnRH and pituitary TSH secretion. To test the hypothesis that prolactin suppresses GnRH and TSH secretion in women, as preliminary evidence that a short-feedback dopamine loop also operates in the human, the effect of hyperprolactinemia on GnRH and TSH secretion was examined. METHODS: Subjects (n=6) underwent blood sampling every 10 min in the follicular phase of a control cycle and during a 12-hour recombinant human prolactin (r-hPRL) infusion preceded by 7 days of twice-daily subcutaneous r-hPRL injections. LH and TSH pulse patterns and menstrual cycle parameters were measured. RESULTS: During the 7 days of r-hPRL administration, baseline prolactin increased from 16.0+/-3.0 to 101.6+/-11.6 microg/l, with a further increase to 253.7+/-27.7 microg/l during the 12-hour infusion. LH pulse frequency decreased (8.7+/-1.0 to 6.0+/-1.0 pulses/12 h; p<0.05) with r-hPRL administration, but there were no changes in LH pulse amplitude or mean LH levels. There were also no changes in TSH pulse frequency, mean or peak TSH. The decreased LH pulse frequency did not affect estradiol, inhibin A or B concentrations, or menstrual cycle length. CONCLUSION: These studies demonstrate that hyperprolactinemia suppresses pulsatile LH secretion but not TSH secretion and suggest that GnRH secretion is sensitive to hyperprolactinemia, but that TSH secretion is not. These data further suggest that the degree of GnRH disruption after 7 days of hyperprolactinemia is insufficient to disrupt menstrual cyclicity.     

Baroreceptor-mediated suppression of osmotically stimulated vasopressin in normal humans

Increases in central venous pressure and arterial pressure have been reported to have variable effects on normal arginine vasopressin (AVP) levels in healthy humans. To test the hypothesis that baroreceptor suppression of AVP secretion might be more likely if AVP were subjected to a prior osmotic stimulus, we investigated the response of plasma AVP to increased central venous pressure and mean arterial pressure after hypertonic saline in six normal volunteers. Plasma AVP, serum osmolality, heart rate, central venous pressure, mean arterial pressure, and pulse pressure were assessed before and after a 0.06 ml.kg-1.min-1-infusion of 5% saline give over 90 min and then after 10 min of 30 degrees head-down tilt and 10 min of head-down tilt plus lower-body positive pressure. Hypertonic saline increased plasma AVP. After head-down tilt, which did not change heart rate, pulse pressure, or mean arterial pressure but did increase central venous pressure, plasma AVP fell. Heart rate, pulse pressure, and central venous pressure were unchanged from head-down tilt values during lower-body positive pressure, whereas mean arterial pressure increased. Plasma AVP during lower-body positive pressure was not different from that during tilt. Osmolality increased during the saline infusion but was stable throughout the remainder of the study. These data therefore suggest that an osmotically stimulated plasma AVP level can be suppressed by baroreflex activation. Either the low-pressure cardiopulmonary receptors (subjected to a rise in central venous pressure during head-down tilt) or the sinoaortic baroreceptors (subjected to hydrostatic effects during head-down tilt) could have been responsible for the suppression of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cortisol inhibits ACTH but not the AVP response to hypoxaemia in fetal lambs at days 123-128 of gestation

During acute hypoxemia in fetal sheep the elevation in ACTH concentration in the fetal circulation at days 125-129 is greater than that at term, but similar rises in AVP occur at both times. To examine whether the diminished ACTH response is due to elevated endogenous cortisol, and if there is differential control of ACTH and AVP release in hypoxemia, we infused either vehicle or cortisol (5 micrograms/min) into fetal sheep at days 123-128 for 5 h before and then during a 2-h period of acute hypoxemia (mean PaO2 decrease 8.2 mmHg) without acidemia. During cortisol infusion, plasma cortisol rose to 40-50 ng/ml, similar to values in term fetuses. In vehicle-infused fetuses, cortisol rose from 2.1 to 7.0 ng/ml at +1 to +2 h of hypoxemia. ACTH rose significantly during hypoxemia in the vehicle-infused fetuses, and this response was attenuated by cortisol infusion. In contrast, fetal AVP rose significantly during hypoxemia both in the presence and absence of cortisol infusion. Fetal breathing movements, and electroocular activity decreased during hypoxemia, and these responses were not altered by cortisol. We conclude that cortisol exerts differential negative feedback on ACTH but not on AVP release during hypoxemia. The maintained AVP response may facilitate cardiovascular adjustments of the fetus to hypoxemia even when endogenous cortisol is elevated, such as near term.     

Preferential release of oxytocin in response to vasoactive intestinal polypeptide in rats

Vasoactive intestinal polypeptide (VIP) was infused into the aorta of pentobarbitone-anesthetized rats (n = 12) in stepwise increasing doses of 0.001 to 10 micrograms/rat at rates varying from 0.3 pmol/min/kg to 3000 pmol/min/kg over 3 min. Blood was withdrawn from the vena cava inferior for the measurement of oxytocin (OT) and vasopressin (AVP) by RIA. The loss of blood was compensated for by infusion of isotonic saline (0.9% NaCl with 0.5% human serum albumin). Control rats received this solution only (n = 11). VIP infusions resulted in a dose-dependent increase in plasma OT which was significantly greater than the slight rise observed in the controls. The difference from controls was significant at infusion rates of 3 pmol/min/kg and more. Plasma AVP, on the other hand, did not rise in response to VIP infusions until the infusion rate was increased to 300 and 3000 pmol/min/kg. At these infusion rates, the increments in AVP were much smaller than those of OT, the levels during the highest infusion rates rising to 8.6 +/- 2.8 and 27.2 +/- 4.8 microU/ml, respectively (log normal means). The preferential release of OT in response to exogenous VIP in rats differs from the response in cats where intracarotid administration of VIP resulted in the release of proportionately more AVP than OT. Immunoreactive VIP is found in the hypothalamo-neurohypophyseal system of rats in close proximity of some of the magnocellular neurons as well as within the nerve terminals. This, together with our data, suggests that endogenous VIP may participate in the release mechanism for OT in rats.