Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP).

We studied the effects of chronic nocturnal hypoxaemia due to obstructive sleep apnoea syndrome (OSAS) on the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-testicular axes and on catecholamine and cortisol secretion. We investigated whether hormones other than catecholamines may serve as markers for chronic hypoxic stress and the possible effects of nasal continuous positive airway pressure (nCPAP) treatment on endocrine status. Nocturnal oximetry was performed in 16 male patients with OSAS diagnosed by polysomnography, immediately before nCPAP treatment and in 11 of the patients the oximetry was repeated after 7 months of nCPAP therapy. Plasma and urinary catecholamines, luteinizing hormone (LH) testosterone, cortisol, thyroid stimulating hormone (TSH), prolactin (PRL), and the response of TSH and PRL to a thyroid releasing hormone (TRH) challenge test were measured immediately before and after 7 months of nCPAP treatment. Subnormal LH and TSH and elevated serum cortisol as well as increased nocturnal urinary norepinephrine levels were found in patients prior to treatment; otherwise endocrine values were normal. There was a significant correlation between low pretreatment nocturnal arterial oxygen saturation and high plasma and urinary norepinephrine levels. The nCPAP treatment caused significant reduction in serum prolactin and TSH, and significant reduction in plasma epinephrine and urinary norepinephrine. The reduction in serum TSH and urinary norepinephrine was most pronounced in the subjects with the worst pretreatment nocturnal hypoxaemia. No other significant changes were found in basal hormone levels. The response to TRH challenge was normal before and after treatment and was not influenced by CPAP therapy. OSAS is associated with elevated catecholamine and cortisol and decreased TSH and LH levels but a normal response to TRH challenge and a normal androgen status. Apart from catecholamines, none of the hormones studied is likely to serve as a specific marker for chronic hypoxic stress.     

Effect of gestational mastectomy on postpartum gonadotropin releasing hormone and thyrotropin releasing hormone-induced luteinizing hormone and prolactin response in first lactation Holstein cattle

First lactation Holstein cows were divided into two treatment groups to evaluate thyrotropin releasing hormone (TRH, 0.25 microgram/kg body weight) and gonadotropin releasing hormone (GnRH; 200 micrograms) induced secretion of prolactin (PRL) and luteinizing hormone (LH) on days 7 and 16 postpartum. Disregarding treatment, LH response was greater (p less than 0.01) on day 16 than day 7 postpartum (7.5 +/- 0.3 ng/ml on day 7 vs 10.2 +/- 0.3 ng/ml serum on day 16). Mastectomized cattle had similar time for initiation of LH increase, but peak concentrations were achieved later. Peak PRL concentrations were reached 12 to 15 min after injection and returned to baseline within 2.5 h in both groups. However, intact cows had higher (p less than 0.01) mean serum PRL than the mastectomized cows for 1 h following injection. Peak PRL concentration was 83.3 +/- 17.6 ng/ml for mastectomized cows vs 128.0 +/- 24.7 ng/ml for intact cows. It appears that udder removal allows for greater pituitary responsiveness to GnRH but diminishes PRL response to TRH suggesting the mammary gland differentially affects pituitary secretion of LH and PRL.     

Normal pituitary function and reserve after selective transsphenoidal removal of a thyrotropin-producing pituitary adenoma

A 37-yr-old woman with recurrent hyperthyroidism after partial thyroid ablation was found to have an enlarged sella turcica and elevated serum thyrotropin (TSH) and prolactin (PRL) levels measured by radioimmunoassay. Serum growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cortisol levels were within normal limits and responded appropriately to provocative stimuli both before and after surgery. Preoperatively, the administration of thyrotropin-releasing hormone (TRH) (200 μg i.v.) and metoclopramide (MCP) (10 mg p.o.) induced a more than twofold increase in serum PRL levels, whereas TSH was only modestly affected. Bromocriptine (2.5 mg p.o.) and l-dopa (500 mg p.o.) suppressed TSH and PRL values to less than 50% of their initial values. After selective transsphenoidal removal of a pituitary adenoma, signs and symptoms of hyperthyroidism disappeared and TSH and PRL returned to normal. The postoperative administration of TRH and MCP produced a normal response for both PRL and TSH. Postoperatively, bromocriptine induced a parallel decrease in the serum level of both hormones, whereas l-dopa decreased PRL but had no effect on the serum TSH level. This case provides evidence that hyperthyroidism caused by a pituitary adenoma can be successfully treated by transsphenoidal surgery with preservation of normal pituitary function and reserve.     

Consequence of dynorphin-A administration on anterior pituitary hormone concentrations in the adult male rhesus monkey

This study examines the role of dynorphin-A(1-13) and dynorphin-A(1-10)-amide in the neuroendocrine regulation of anterior pituitary hormones in nonrestrained, adult male rhesus monkeys. The effects of these opioids on plasma concentrations of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH) and growth hormone (GH) were assessed. Intravenous administration of dynorphin-A(1-13), 1-120 micrograms/kg, significantly increased plasma PRL levels. Average maximal increases of 90-230% occurred within 5 min and levels remained significantly elevated for up to 120 min. PRL response reached a plateau following the 30 micrograms/kg dose. Dynorphin-A(1-13) had no observable effects on plasma concentrations of LH, FSH, TSH or GH at any dose level studied. Administration of dynorphin-A(1-10)-amide produced significant dose-dependent increases in plasma PRL concentrations. Dose levels of 1-120 micrograms/kg produced mean peak increases from 100 to 230%, 5-10 min postadministration. Dynorphin-A(1-10)-amide had no significant effect on plasma concentrations of LH, FSH, TSH or GH. The increases in plasma PRL concentrations induced by dynorphin-A were naloxone-reversible. These results indicate a selective effect of dynorphin-A on the regulatory mechanisms of PRL secretion over that of other anterior pituitary hormones.     

Dissociation of prolactin responsiveness to TRH and chlorpromazine in women with isolated gonadotropin deficiency.

The hormonal response to luteinizing hormone releasing hormone (LHRH) thyrotropin releasing hormone (TRH) and chlorpromazine has been evaluated in eleven female subjects with the syndrome of isolated bihormonal gonadotropin deficiency (IGD). Following LHRH, all subjects had elevations of both LH and FSH, but the gonadotropin responses were attenuated relative to those observed in normal female subjects studied in the early proliferative phase of the cycle. Similarly, peak TSH levels after TRH were significantly less in subjects with IGD relative to normal controls. Basal prolactin levels were low in the patient group. Prolactin levels following TRH increased at least two-fold in control subjects and in the group with IGD. Conversely, chlorpromazine failed to induce elevations of prolactin in eight of nine females with IGD.     

Reduction of plasma gonadotropin levels and pituitary tumor size by treatment with bromocriptine in a patient with gonadotropinoma.

A pituitary tumor with suprasellar extension was found by magnetic resonance imaging (MRI) in a male with diabetes mellitus. Endocrine examination revealed high plasma follicle-stimulating hormone (FSH) and alpha-subunit levels, which increased with administration of thyrotropin (TSH)-releasing hormone (TRH). Plasma luteinizing hormone (LH) and testosterone levels were low. Pituitary gonadotropin producing tumor was diagnosed. Because the patient refused surgery, bromocriptine was administered and plasma FSH and alpha-subunit rapidly decreased; on MRI the tumor size was gradually reduced. When pituitary operation is not feasible, bromocriptine is one choice of treatment.     

Hypothalamic origin of idiopathic hypopituitarism

Two adult male patients with anterior pituitary insufficiency of unknown etiology were studied during acute challenge with thyrotropin releasing hormone (TRH) and aqueous vasopressin (AVP). Each patient had previously documented thyrotropin (TSH) adrenocorticotropin (ACTH) and gonadotropin deficiencies dating back to childhood. Plasma growth hormone (GH) was undetectable in each following insulin and arginine stimuli. Intravenous administration of synthetic TRH produced in both patients a prompt rise in serum TSH similar to the response observed in normal subjects. AVP injection was followed by a significant elevation of plasma 17-hydroxycorticosteroids in each patient and a rise in plasma GH in one of them. These results demonstrate that the adenohypophysis of these two patients could respond to stimuli of hypothalamic origin. It is concluded that the anterior pituitary failure was due to a deficiency of hypothalamic “releasing factors” caused by a disorder of hypothalamic function of unknown etiology.     

Studies on pulsatile secretion of thyrotropin and prolactin in hypogonadal women

Studies of normal human subjects have shown that prolactin (PRL) as well as thyrotropin (TSH) are secreted in pulsatile fashion. This study was designed to investigate whether or not these two hormones are secreted synchronously. Ten postmenopausal women who had had amenorrhea for at least 3 years and 2 women who had been ovariectomized 3 and 5 years before and were between 35 approximately 60 yr of age were studied. Blood samples were obtained between 1500 approximately 2000 h at 15 min intervals. Distinct pulsatile fluctuation of plasma TSH concentration was present in all subjects. However, only 31% of these pulses were observed to coincide with PRL pulses. The mean (+/- SD) increment of TSH (nadir to peak) was 1.2 +/- 0.5 mu u/ml. The mean interval between pulses of TSH was 73 min. In contrast, regular episodic fluctuation of plasma PRL concentration were present in only 5 out of 12 women, and 48% of these pulses were observed to coincide with TSH pulses. These results indicate that pulses of TSH and PRL are generated independently. Since thyrotropin-releasing hormone (TRH) may be a direct generator of TSH pulse and a potent stimulator of PRL secretion, our results may suggest that physiological concentration of TRH in portal blood which is sufficient to elicit TSH pulse may be too low to elicit PRL pulse.     

Hypothyroidism and amenorrhea due to hypothalamic insufficiency. A study in four young women.

Four women, aged 17 to 23, were evaluated for secondary amenorrhea of 12 to 36 months' duration. All were considered to have hypothalamic hypothyroidism on the basis of low thyroxine (T4) concentrations, inappropriately low thyrotropin (TSH) levels, with a normal TSH response to thyrotropin-releasing hormone (TRH, 500 microgram intravenously) in three, and absence of a pituitary lesion. Nevertheless, menses did not resume after adequate replacement with thyroid hormone. Investigation of the pituitary-gonadal axis revealed a normal increase in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) following the intravenous administration of gonadotropin-releasing hormone (GnRH). Three subjects received clomiphene citrate, 100 mg/day for five days, but a normal menstrual cycle was not induced. It is concluded that the amenorrhea was not due to thyroid hormone deficiency but, like the hypothyroidism, to a hypothalamic abnormality involving secretion of the appropriate releasing hormone.     

THE INTERACTION OF GROWTH HORMONE RELEASING HORMONE WITH OTHER HYPOTHALAMIC HORMONES ON THE RELEASE OF ANTERIOR PITUITARY HORMONES

To determine whether the 29 amino-acid fragment of growth hormone releasing hormone (GHRH) can be combined with other hypothalamic releasing hormones in a single test of anterior pituitary reserve, the responses of anterior pituitary hormones to combinations of an i.v. bolus of GHRH(1-29)NH2 or saline with an i.v. bolus of either LH releasing hormone (LHRH) plus TRH, ovine CRH(oCRH) or saline were studied. Each infusion of GHRH(1-29)NH2 resulted in a rapid increment of the plasma GH value. Infusion of GHRH(1-29)NH2 also caused a small and transient rise in plasma PRL, but no change in the integrated PRL response. The combination of GHRH(1-29)NH2 with LHRH plus TRH caused a larger increment of peak and integrated plasma TSH levels than LHRH plus TRH alone. GHRH(1-29)NH2 did not affect the release of other anterior pituitary hormones after infusion with oCRH or LHRH plus TRH. Because of the finding of potentiation of the TSH-releasing activity of LHRH plus TRH by GHRH(1-29)NH2, the study was extended to the investigation of TSH release after infusion of TRH in combination with either GHRH(1-29)NH2 or GHRH(1-40). In this study the combination of TRH with both GHRH preparations also caused a larger increment of the peak and integrated plasma TSH levels than TRH alone. It is concluded that GHRH(1-29)NH2 possesses moderate PRL-releasing activity apart from GH-releasing activity. In addition, GHRH potentiates the TSH-releasing activity of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pituitary autonomy in hyperprolactinemic secondary amenorrhea: results of hypothalamic-pituitary testing.

Twenty-seven women with secondary amenorrhea of greater than six months duration were subjected to multiple testing of hypothalamo-pituitary function. They were divided into normo-prolactinemic (Group 1 mean serum prolactin (PRL) 9.8 ng/ml; range 6.8 to 13.0 ng/ml; n=9) and hyperprolactinemic (Group 2 mean 37.5 ng/ml; range 19.2 to 93.7 ng/ml; n=18) groups on the basis of 4 weekly baseline determinations. Group 2 had significantly (P less than .05) lower serum LH and urinary pregnanediol levels than did Group 1; there was no statistical difference between the groups in serum FSH, T4, T3 or urinary estrogen measurements. Two women in Group 2 were found to have a pituitary chromophobe adenoma. Group 2 women showed no significant rises in serum PRL following stimulation tests with thyrotropin releasing hormone (TRH, 200 microng iv) and metoclopramide (10 mg orally), which caused significant responses in Group 1. The TSH response to TRH was, however, preserved in Group 2, while it was subnormal in Group 1 subjects. Both groups showed similar FSH and LH responses to luteinizing hormone-releasing hormone (LHRH, 25 microng iv). No significant suppression of serum PRL was seen in Group 2 patients given L-Dopa (500 mg orally),, which produced a significant response (P less than 0.05) in Group 1 subjects, while all patient showed marked reduction in serum PRL values following 2-bromo-alpha-ergocryptine (CB-154, 2.5 mg orally). When compared with other Group 2 members, the 2 cases with proven pituitary adenomata gave similar responses to the stimulation-inhibition tests and were not clearly distinguished on this basis. We conclude: 1. The pattern of PRL responses to dynamic tests, although of pathophysiological interest an autonomous pituitary lesions in patients with hyperprolactinemic secondary amenorrhea. 2. Such dynamic tests, although a pathophysiological interest, provide no clinical information additional to that provided by the mean basal serum PRL value. 3. In clinical practice, such dynamic tests should be confined to patients with mean serum PRL levels at around the upper limit of the normal range.     

Selectivity of melatonin pituitary inhibition for luteinizing hormone-releasing hormone

The pineal indole melatonin suppresses the neonatal rat luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses to LH-releasing hormone (LHRH), as shown in previous studies from this laboratory. We show in this study that the melatonin inhibition is a selective effect and is not due to general inhibition of pituitary function. The effects of the indole on the responses to thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) and on basal pituitary hormone secretion were examined with cells in culture. Neonatal rat anterior pituitary cells dissociated with collagenase and hyaluronidase were cultured overnight and distributed to 35-mm dishes at the time of use. For examination of melatonin effects on the response to releasing hormones, the cells were incubated for 3 h in control medium or medium containing LHRH (10-9-10-6 M), TRH (10-10-10-6 M), or SRIF (10-9-10-6 M), either alone or in the presence of melatonin (10-8 or 10-6 M). For examination of basal hormone secretion, the cells were incubated for 1.5, 3, 6, 15, or 24 h in either medium alone or medium containing melatonin (10-6 M). Medium and cell lysate concentrations of LH, FSH, thyroid-stimulating hormone (TSh), prolactin (PRL) and growth hormone (GH) were determined by double antibody RIA. As previously, melatonin (10-8 M) significantly suppressed LH and FSH release by all concentrations of LHRH. This concentration of the indole produced maximal suppression of both LH and FSH responses to LHRH. By contrast, melatonin at a 100-fold greater concentration (10-6 M) had no effect on TRH stimulation of TSH or PRL release or on SRIF inhibition of GH release. Similarly, melatonin had no effect on basal release of TSH, PRL, or GH at the times examined. These findings show that melatonin inhibition of the gonadotroph response to LHRH is a selective effect.     

Osmotic control of the release of prolactin and thyrotropin in euthyroid subjects and patients with pituitary tumors.

The effects of acute changes in serum osmolality on basal serum PRL and TSH levels and on responses of prolactin (PRL) and thyrotropin (TSH) to the thyrotropin-releasing hormone (TRH) analogue, N3im-methyl-TRH, were studied in ten euthyroid subjects and in three patients with PRL-secreting pituitary tumors. An oral water load of 20 ml/kg had no effect on basal serum PRL or TSH levels but did result in an increased PRL response to methyl-TRH in the ten euthyroid patients. Intravenous infusion of 5% sodium chloride in the ten euthyroid subjects significantly depressed basal serum PRL levels but had no effect on the PRL response to methyl-TRH. Infusion of hypertonic saline significantly decreased the TSH response to methyl-TRH. In the three patients with pituitary tumors, oral water loading and hypertonic saline infusion had no significant effect on the basal serum PRL and TSH or the PRL and TSH responses to methyl-TRH. The patients with pituitary tumors had a higher basal serum osmolality and a proportionately higher serum concentration of arginine vasopressin than the euthyroid patients. These data suggest that changes in osmolality in euthyroid patients may have a direct effect on the anterior pituitary's PRL and TSH response to a releasing factor.     

Thyrotropin and gonadotropin releasing hormones (TRH and GnRH) do not alter levels of oxytocin and oxytocin does not change the response of luteinizing or follicle stimulating hormones to GnRH in humans

Four hundred micrograms of synthetic thyrotropin releasing hormone (TRH) were given intravenously to 4 normal men and 4 normal women, and four weeks later, 1000 micrograms of TRH were administered intravenously to 4 of the 8 individuals and oxytocin (OT) was measured in plasma on both occasions. Following injection of either dose of TRH, OT did not change significantly from baseline. Likewise, synthetic gonadotropin releasing hormone (GnRH), 100 micrograms, administered intravenously to 6 normal men did not alter the levels of OT from baseline. Synthetic OT, 300 mU/minute, administered 30 minutes before and for 90 minutes after injection of GnRH, was without effect on the GnRH-induced rise of luteinizing hormone (LH) or follicle stimulating hormone (FSH) in normal men. We conclude that continuous infusion of OT in pharmacologic concentrations does not alter the pituitary release of LH or FSH in response to GnRH in humans. TRH and GnRH given intravenously do not alter basal levels of OT in the plasma of humans, thus a physiologic role for GnRH or TRH in the neuroendocrine control of OT secretion in humans is unlikely.     

Pituitary vasoactive intestinal peptide regulates prolactin secretion in the hypothyroid rat

In this study, we demonstrated that the cell content and basal secretion of vasoactive intestinal peptide (VIP) in primary rat pituitary cell cultures were increased in hypothyroidism. VIP release from hypothyroid pituitary cells in vitro was stimulated by thyrotropin releasing hormone (TRH 10(-8) to 10(-6) M) and growth hormone (GH)-releasing hormone (GHRH 10(-9) to 10(-8) M) but not by corticotropin-releasing hormone or luteinizing hormone-releasing hormone in concentrations up to 10(-6) M. In the presence of anti-VIP antisera, there was a significant decrease in basal prolactin secretion from cultured hypothyroid pituitary cells (p less than 0.005) indicating that VIP exerts a tonic stimulatory effect on prolactin (PRL) secretion. The increment in PRL secretion following TRH was not affected by exposure to anti-VIP indicating that PRL release after TRH is not mediated by VIP at the pituitary level. In contrast to changes in PRL, exposure to anti-VIP had no effect on basal GH secretion, indicating that the PRL changes are hormone specific. Similarly, GHRH-induced GH release was unaffected by VIP immunoneutralization.     

Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors.

Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.     

PROLACTIN AND LUTEINIZING HORMONE PROFILES OF CURED ACROMEGALIC SUBJECTS

The 24-h PRL and LH hormone profiles were analysed of 16 cured male acromegalic patients who had undergone selective transsphenoidal surgery 4-9 years previously. Eight of these patients also underwent pituitary irradiation. Blood samples were taken at 20-min intervals; the PRL and LH data were analysed with the cluster program. ARIMA modelling, cross-correlation techniques, Fourier analysis, and cosinor analysis. About 10-11 PRL and LH peaks were demonstrated for both non-irradiated and irradiated patients. The absolute heights of PRL pulses and the mean valley levels were significantly greater for irradiated patients than for non-irradiated patients, but the increment in amplitude did not differ. A significant diurnal rhythm for PRL was found for all non-irradiated patients but for only one irradiated patient. LH pulse area and amplitude were lower in the group of irradiated patients. The incremental responses of LH and PRL to GnRH and TRH, respectively, were lower in irradiated patients than in non-irradiated patients. During the night (0200-0800 h) the number of PRL pulses decreased in non-irradiated patients but not in irradiated patients. Pulse nadirs and amplitudes increased during the evening and night in non-irradiated patients but were constant in irradiated subjects. Bivariate modelling of the data for 14 patients revealed significant cross-correlations between LH and PRL pulses in nine subjects. This study demonstrates that the pulsatile secretion of PRL and LH in treated acromegalics is basically normal. Additional radiation therapy, however, may lead to damage of the hypothalamus, as reflected by the absence of a circadian PRL rhythm. A direct influence on the pituitary by radiation is indicated by the decreased magnitude of LH pulses and the diminished response of LH and PRL after injection of GnRH and TRH, respectively.     

Apomorpine inhibits the prolactin but not the TSH response to thyrotropin releasing hormone.

Pretreatment of normal subjects with apomorphine, a dopamine receptor agonist, resulted in significant impairment of the subsequent prolactin (PRL) response to thyrotropin releasing hormone (TRH). The mean maximal increment of PRL was 27.9+/-2.4 ng/ml after TRH alone, and 11.9+/-3.0 ng/ml (P less than 0.001) after apomorphine plus TRH. In contrast, the.thyrotropin (TSH) response to TRH was unaffected by apomorphine (10.5+/-2.9 vs. 9.5+/-1.8 muU/ml, P greater than 0.5). These results demonstrate that dopaminergic effects are capable of inhibiting PRL responses to TRH, probably via a direct effect on the lactotrope cell. They also suggest that dopaminergic influences are not important in the regulation of TSH secretion.     

EFFECT OF LOW-DOSE DOPAMINE INFUSION ON BASAL AND STIMULATED TSH AND PROLACTIN CONCENTRATIONS IN MAN

Dopamine (DA) infused at pharmacological doses in man inhibits thyrotrophin (TSH) secretion, although the physiological significance of this observation is unclear. The effect of low-dose DA infusion (0.1 microgram/kg/min) on TSH and prolactin (PRL) concentrations during stimulation with thyrotrophin releasing hormone (TRH) in normal male subjects is reported. Six subjects were given intravenous DA or placebo infusions for 165 min on separate days. A bolus of TRH (7.5 micrograms) was given at + 90 min, followed by infusion of the tripeptide (750 ng/min) for 45 min during both DA and placebo studies. In all subjects TRH administration caused a small rise in TSH which was partially inhibited by DA (peak 5.73 +/- 0.85 mU/l vs 4.58 +/- 1.09, P less than 0.05). PRL response to TRH was almost totally inhibited by DA (620 +/- 164 mU/l vs 234 +/- 96, P less than 0.05); integrated TSH and PRL responses to TRH were similarly inhibited by DA. Circulating plasma DA concentration during infusion of the catecholamine was 3.46 +/- 1.00 ng/ml, which is within the range reported in pituitary stalk plasma of other species. These data support the hypothesis that DA is a physiological modulator of TSH secretion in normal man. Major differences in the time course of TSH and PRL responses to TRH, and in the suppressive effect of DA on these responses suggest that there are fundamental differences in stimulus-secretion coupling for TRH and the lactotroph and thyrotroph.