Thyrotropin-releasing Hormone Infusion Research Articles

Different prolactin, thyrotropin, and thyroxine responses after prolonged intermittent or continuous infusions of thyrotropin-releasing hormone in rhesus monkeys.

Serum PRL, TSH, and T4 secretion during prolonged continuous or intermittent iv infusions of TRH were studied in 14 adult ovariectomized rhesus monkeys (Macaca mulatta). For 9 days, TRH was administered intermittently at 0.33 or 3.3 micrograms/min for 6 of every 60 min and continuously at 0.33 micrograms/min. With both modes, the PRL levels and responsiveness to TRH simulation peaked on day 1 and then fell to levels that were still higher than the preinfusion values; levels for the intermittently treated group on days 3-9 were 2- to 4-fold above prestimulation levels and significantly (P less than 0.01) higher than levels for the continuously treated group. Elevated basal levels and PRL responses to TRH pulses were similar during the 0.33 and 3.3 micrograms/min pulses of the 9-day treatment period. For both TRH modes, TSH levels were elevated significantly (P less than 0.001) on day 1 [this increase was higher with continuous infusion (P less than 0.001)] and then fell to preinfusion levels by day 3. Serum T4 also increased during both continuous and intermittent TRH stimulations. However, serum T4 levels were significantly lower (P less than 0.01) after intermittent TRH (both 0.33 and 3.3 micrograms/min) than after continuous (0.33 micrograms) TRH (8 +/- 1.1 and 10 +/- 1.8 micrograms T4/dl vs. 18 +/- 3.1 micrograms, respectively). These PRL and T4 responses were replicated when the mode of administering 0.33 micrograms/min TRH was reversed after 9 days. An iv bolus of TRH (20 micrograms) after 9 days of continuous or intermittent TRH infusion caused significant release of PRL and TSH, an indication that neither mode of administration resulted in pituitary depletion of releasable hormone. We have concluded that intermittent TRH is more effective in elevating serum PRL, and continuous TRH is more effective in raising TSH and T4 levels. Thus, the manner of TRH secretion by the hypothalamus may determine its relative physiological importance in the stimulation of lactotropes and thyrotropes.

Effects of infusion of thyrotrophin releasing hormone and dopamine either alone or in combination on plasma prolactin concentrations in the anoestrous ewe.

Plasma concentrations of prolactin in anoestrous ewes were respectively lowered or raised by the separate infusion of dopamine or thyrotrophin releasing hormone (TRH). Combined treatment with dopamine and TRH lowered the concentration of prolactin in plasma but the values increased markedly after the treatment was stopped and reached a level equivalent to that found in ewes treated with TRH alone. The results are interpreted as evidence that both dopamine and TRH play a regulatory role in determining the secretion of prolactin in the ewe.

The TRH stimulation test in subtypes of unipolar depression

The thyrotropin releasing hormone (TRH) stimulation test was administered to 54 primary unipolar endogenously depressed and 19 non-depressed hospitalized inpatients. Blunted TSH reponses to TRH infusion (Δ max TSH<7 μU/ml) were revealed in 18 depressed and no non-depressed patients ( P<0.01). Augmented TSH responses (Δ max TSH>23 μU/ml) were noted in 8 depressed and no non-depressed patients ( P = n. s.). The TRH stimulation test did not distinguish between subtypes of unipolar depression using the familial subtyping criteria of Winokur. These findings are discussed in light of previously reported dexamethasone suppression test subtype distinctions.

Diurnal hormonal responses to thyrotropin-releasing hormone in normal men

Bolus injections of synthetic thyrotropin-releasing hormone (TRH) were administered to five young normal men in the morning (0900 hr) and the evening (1800 hr) on different days. Frequent blood samples for prolactin (PRL) and TSH analyses were collected before and after TRH infusion. Although there were no differences between the morning and the evening basal PRL levels, a significantly greater PRL response to TRH in the evening was observed (Δ PRL, a.m. vs p.m., p < 0.025). Since TRH stimulates PRL through a direct effect on the pituitary, our data suggest that there is a diurnal variation in the pituitary lactotroph responsiveness to TRH. On the other hand, a.m. and p.m. basal and TRH-stimulated TSH responses were virtually identical.

THYROID HORMONE RESPONSE TO THYROTROPIN RELEASING HORMONE BY PIGS FED CANOLA, RAPESEED OR SOYBEAN MEALS

Pigs weighing approximately 13 kg were fed diets in which the protein supplement was either 12% soybean meal (SBM), 15% canola meal (CM), or 15% rapeseed meal (RSM). The CM and RSM originated from the cultivars Tower and Midas, respectively. After 46–59 days on the experimental diets, blood samples were collected via jugular catheters at −10, 0 and for 70 min following the infusion of 40 μg thyrotropin-releasing hormone (TRH). The preinfusion level of plasma thyroxine (T4) was depressed (P &lt; 0.01) in the RSM-fed pigs when compared to the SBM- and CM-fed animals (1.8 vs. 3.7 and 3.6 μg/dL, respectively). Following TRH infusion, circulating triiodothyronine increased for each diet (P &lt; 0.05) with no difference among diet groups. Plasma T4 concentrations did not increase following TRH infusion in pigs fed CM or RSM whereas SBM-fed pigs increased the circulating T4 from 3.7 to 4.9 μg/dL (P &lt; 0.001), indicating that CM- or RSM-fed pigs had no detectable ability to increase the output of T4 in response to an external TRH stimulus. It is suggested that further studies on the use of CM in swine diets are required under conditions which require increased thyroid hormone secretion.

Thyrotropin-releasing hormone inhibits pancreatic enzyme secretion in humans

Recent studies have shown that thyrotropin-releasing hormone is present in gastrointestinal tissues and has effects on gastrointestinal motility and secretion. In the present study, we have investigated in healthy subjects the effects of various doses of thyrotropin-releasing hormone on secretin-cholecystokinin-stimulated pancreatic secretion. Intravenous infusion of thyrotropin-releasing hormone at doses of 4, 20, and 100 μg/30 min, administered during a constant pancreatic stimulation with secretin (0.5 Clinical Units/kg/h) and cholecystokinin (0.5 Ivy dog units/kg/h), produced a significant decrease in lipase and chymotrypsin secretion without affecting volume and bicarbonate secretion. The decrease appeared immediately with the lowest dose of TRH employed, and was progressively more marked with increasing doses of the hormone. Compared with the control experiments, the maximal inhibition of lipase output reached −17.6%, −37.2%, and −43%, and the maximal inhibition of chymotrypsin output −18.2%, −39.3%, and −44.9%, for the three doses of thyrotropin-releasing hormone employed, respectively. It is concluded that TRH has a marked inhibitory effect on the enzymatic component of the pancreatic secretion stimulated by submaximal doses of secretin and cholecystokinin. The physiologic importance of this effect remains to be defined.

Relactation by Mothers of Sick and Premature Infants

Relactation, the induction of lactation at any time beyond the immediate postpartum period, has received minimal scientific investigation. In this study, one adoptive mother and six mothers ten to 150 days postpartum, who for a variety of reasons did not initiate or maintain lactation after delivery, attempted relactation. Each suckled her infant at regular feeding intervals. Prior to milk production, formula was provided during suckling through an artificial device. Serum prolactin responses to thyrotropin-releasing hormone infusion and to suckling were measured at the start of the study and to suckling at approximately weekly intervals thereafter. All mothers produced milk; three completely nourished their infants and two others provided at least half of their infants' nutritional needs. The adoptive mother and one other failed to provide significant quantities of milk. Mothers reached their maximum potential for milk production in varying periods of time (eight to 58 days). Shorter postpartum interval and less postpartum breast involution correlated with the likelihood of successful relactation and the rapidity of the onset of lactation. Basal prolactin levels and stimulation tests were of no additional predictive value. Each mother, regardless of milk production, expressed positive feelings about nurturing her infants in this manner. We conclude that relactation frequently is possible and may offer the mother of a sick or premature infant who desires to breast-feed an alternative if she does not maintain lactation in the immediate postpartum period.

Thyroid stimulating hormone and growth hormone responses to thyrotropin releasing hormone in anorexia nervosa.

Ten female patients who satisfied objective criteria for the diagnosis of anorexia nervosa were given 500 microgram of thyrotropin releasing hormone. Thyroid stimulating hormone and growth hormone responses were measured in duplicate by radioimmunoassay. These patients had a low normal delta thyroid stimulating hormone but a delayed peak response. In addition, these patients had pathological growth hormone release in response to thytotropin releasing hormone infusion. Both delayed peak thyroid stimulating hormone and growth hormone response to thyrotropin releasing hormone have been reported for patients with hypothalamic disorders.

The influence of long-term low dose thyrotropin-releasing hormone infusions on serum thyrotropin and prolactin concentrations in man.

The purpose of the present study was to evaluate in man the relative thyrotroph and lactotroph response to a 48-h low dose constant TRH infusion. Before, during, and after the 75 ng/min TRH constant infusion, serum samples were obtained every 4 h in six euthyroid ambulating male subjects for measurements of TSH, PRL, T4, and T3. The TSH response, employing a specific and sensitive human TSH RIA, demonstrated a significant rise from the mean basal pre-TRH value of 2.35 +/- 0.64 microU/ml (+/- SEM) to 3.68 +/- 0.80 (P < 0.005) during the TRH infusion; this value fell below the basal level to 1.79 +/- 0.47 (P < 0.05) post infusion. Serum T4 values were increased above basal both during (P < 0.025) and after (P < 0.025) TRH infusion, whereas serum T3 values were not significantly changed throughout the entire study period. The daily TSH nocturnal surge was augmented in both absolute and relative terms during the first 24 h or the TRH infusion, unchanged during the second 24 h of infusion, and inhibited during the first postinfusion day. Other than a minimal increase in serum PRL during the first few hours of the infusion, no significant alteration in the mean basal concentration or circadian pattern of PRL secretion was evident during or after the low dose TRH infusion. These findings would indicate that 1) near-physiological stimulation of the pituitary with TRH produces a greater stimulation of TSH release than of PRL release and 2) the factor or factors producing the circadian TSH surge may not be mediated through fluctuations in endogenous TRH.

Effect of thyrotropin releasing hormone on the sleep EEG and endocrine profile.

(1) No disturbance in sleep-related electroencephalographic patterns or hormonal profiles was demonstrable following infusion of thyrotrophin releasing hormone in pharmacological dosage in normal Caucasian subjects. (2) This is contrary to findings reported in a recent Japanese study.

Plasma concentration of thyrotropin-releasing hormone, thyrotropin, prolactin, and growth hormone during five-day osmotic pump infusion of thyrotropin-releasing hormone.

Pituitary TSH, PRL, and GH responses to 5-day infusion of TRH using Alzet osmotic minipumps (Alza Corp.) were investigated in two trials to examine comparative hormonal response to continuous stimulation. In each trial, eight (four control and four treatment) ovariectomized ewes were used. The TRH dose infused was 500 μg/day (trial 1) and 100 μg/day (trial 2). Infusion of TRH with osmotic pumps increased mean plasma TRH to 637.8 pg/ml in comparison to 35.2 pg/ml in the untreated control animals in trial 1 and 60.0 vs 9.4 pg/ml in trial 2. On day 1 of trial 1, there was an initial stimulation of mean TSH levels to 12.2 ng/ml, which declined to 4.5 ng/ml during the collection period. A mean concentration of 7.9 ng/ml was observed on day 3. The TSH level on day 5 was 13.4 ng/ml, as compared to 1.6 ng/ml in the control animals throughout trial 1. In trial 2, a similar pattern of TSH secretion was observed. The concentration on day 1 declined from 10.2 to 6.1 ng/ml. The mean concentration on days 3 and 5 ere 9...

A study on endemic goiter in East Java of the Republic of Indonesia (author's transl)

We conducted a medical survey on subjects living in the mountain districts, located at about 400 to 500 m above sea level, near Malang City in the eastern part of Java, the Republic of Indonesia. Serum levels of thyrotropin (TSH) and thyroid hormones were measured in 163 subjects from 9 to 70 years of age, of which 45 were male and 118 were female. A synthesized thyrotropin releasing hormone (TRH) 500pg infusion test was performed on 41 of the subjects from 14 to 70 years of age (7 males, 34 females) and on 15 normal Japanese subjects from 19 to 35 years of age (7 males, 8 females) as controls.Serum TSH and triiodothyronine (T3) were measured by means of radioimmunoassay, serum thyroxine (T4) by competitive protein binding analysis, and serum PBI by the auto-analyser method. The incidence of antithyroglobulin antibody (thyroid test) and antimicrosomal antibody (microsome test) was also studied to assess the role of auto-immunity in goitrogenesis. Goiter size was classified into five grades : from Grade 0 (without goiter) to Grade IV (with huge goiter) by our criteria.Mean serum PBI values were low in all groups with goiters, especially in subjects with huge goiters, but there was no significant difference between non-goitrous and goitrous groups. In one of the 28 non-goitrous subjects, the serum T4 level was low while that of the remaining 27 was within the normal range. Serum T4 values of subjects with big and huge goiters were significantly lower than those of the non-goitrous group. There was no significant difference between the control and non-goitrous groups.On the other hand, serum T3 levels were normal in only two of the 28 non-goitrous subjects and were low in the remaining 26. In the group with huge goiters, serum T3 levels were low in 9, normal in 20, and elevated in only one. T3 values in the groups with big and huge goiters were significantly higher than those of the non-goitrous group. As mentioned above, there was a negative correlation between serum T4 and T3 in subjects with goiters, and relative hypersecretion of T3 occurred in the goitrous groups in contrast to the non-goitrous group. The result of our study confirms that preferential secretion of T3 by the thyroid occurs in goitrous subjects and may represent an important homeostatic mechanism to combat against iodine deficiency.Serum TSH levels in 28 non-goitrous subjects were all within the normal range, and there were elevated serum TSH levels in only 19 out of the 135 goitrous subjects. Although serum log TSH levels do not significantly correlate with the degree of goiter, the mean serum log TSH of the goitrous groups was higher than that of the non-goitrous group, the mean of which was higher than that of the control subjects.Following TRH infusion, 7 non-goitrous subjects showed normal serum TSH response to TRH. In 34 goitrous subjects, there were various serum TSH responses, which included a normal response in 17, delayed in 6, hypo in 4, non in 5 and hyper in 2. According to our results of the TRH test, the secretion of TSH by the pituitary in goitrous subjects following TRH infusion may be different from that in a normal control. There were two inverse relations between basal TSH and T4 (r=-0.43, P<0.01) and peak TSH and T4 (r=-0.44, P<0.01) following TRH infusion. There was, however, no significant relation between serum TSH and T3. Since serum TSH correlated with serum T4 in the TRH test, the TSH secretion of the pituitary may be partially controlled by the serum T4 level. There was no positive case in the thyroid test and only one positive case in the microsome test.Many of the subjects with goiter have hypothyroidism, if judged by serum T4, T3 and PBI.

Thyrotropin and prolactin secretory patterns during 24-hours infusion of thyrotropin-releasing hormone in calves.

Plasma levels of thyrotropin (TSH), prolactin (Prl), growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) were measured in response to continuous 24-h infusion of synthetic thyrotropin-releasing hormone (TRH) in normal and surgically thyroidectomized (THYX) calves in a series of 2 experiments. In the 1st experiment, the low dose of TRH (0.077 microgram/min) had no effect on any hormone levels measured. Plasma TSH concentration increased significantly (p less than 0.05) in response to TRH infusion (0.77 microgram/min) in both experiments, but plasma TSH levels plateaued and then declined in both cases despite continued TRH infusion and irrespective of the presence or absence of a thyroid gland. A similar pattern of secretion, though less markedly decreased over time, was observed for plasma Prl in both experiments. The higher dose (0.77 microgram/min) of TRH had no effect on plasma GH concentration in the 1st infusion, but did result in a significant (p less than 0.05) increase in overall mean concentration of GH in both normal and THYX calves in the 2nd experiment. Removal of the thyroid gland, thus removing the source of increasing T4 and T3 levels seen in normal calves infused with TRH, failed to alter the secretory patterns of TSH and Prl. These data suggest that feedback inhibition by increasing plasma thyroid hormone concentrations was not responsible for the failure of TSH and, to a lesser extent, Prl to maintain chronically elevated plasma levels in response to continuous 24-h TRH infusion. It is suggested that a depletion of pituitary TSH and Prl stores readily secretable in response to a constant dosage level of TRH may be responsible for the secretory patterns observed.

Cytological changes of the pituitary basophils in rats slowly infused with thyrotropin-releasing hormone (TRH).

Young male rats were slowly infused with synthetic TRH, 1 microgram/hr, for 1, 3, 24, 48 and 72 hr, respectively. In the control rats, the basophils of the pituitaries can be divided, in their cytological properties, into the II- (classical thyrotrophs), II/III-,III, (classical LH-cell), and III/IV-type cell. The typical IV-type cells (classical FSH-cell), however, are scarcely found in the young rats. Following 1-hr infusion of TRH, the II-type cells decrease in number with the advancement of granular release, but morphological changes are not yet concrete on the other types of basophils. The II-type cells are quickly invisible following a 3-hr infusion, while the III- and III/IV-type cells remain without any significant changes. The III- and III/IV-type cells are progressively degranulated after a 24-hr infusion. The diameter of secretory granules is reduced to 100--150 nm. The smallest ones below 50 nm in diameter, are disintegrated to disperse into the ground matrix. After degranutlaion, the III/IV-type cells appear to revert to the polygonal or stellate cells with the identical fine structure with the II-type cells. There is evidence that the thyroidectomy cells may develop from the III/IV-type cells only after a 48-hr infusion. After 72 hr, most basophils are provided with the uniform structure of "reversionary II-type cells". In reference to the high serum TSH concentration and no significant change of pituitary TSH concentration under the same experimental condition (Soji, 1978), the present author conclusively postulates that the degranulation of the III/IV-type cells may mainly reflect the conspicuous elevation of serum TSH concentration. The above morphological results are contradictory a plausible view that TRH acts only upon the thyrotrophs to release TSH. The fact that all the basophils ultimately take an appearance of "reversionary II-type cells" in the gland by the prolonged infusion of TRH may not only suggest the share of responsiveness of all the basophils to TRH, but also support the hypothesis of secretory cycle of the basophils.

Ultrastructure of thyroid follicular cells following hypophysial portal vascular infusion of thyrotropin‐releasing hormone

AbstractUltrastructural changes in thyroid follicular cell morphology were studied following the infusion of thyrotropin‐releasing hormone (TRH) for 1 min into a hypophysial stalk portal vessel of adult male rats. At 1, 5, 15 and 30 min following infusion, thyroid glands were removed and prepared for electron microscopic examination. Thyroid follicular cells in unoperated, sham‐operated non‐infused, and saline‐infused control rats were cuboidal, generally lacked intracellular colloid droplets and contained variable numbers of electron‐dense lysosome‐like bodies distributed throughout the cytoplasm. In experimental animals, marked intracellular colloid droplet accumulation was observed 5 min after TRH infusion and remained a constant finding throughout the time‐periods studied. Numerous lysosome‐like dense bodies accumulated in the apical cytoplasm of thyroid follicular cells at 30 min. Fusion of colloid droplets and lysosome‐like bodies had apparently occurred by 30 min. At this time the colloid droplets were smaller, more electron‐dense and were often located more basally within the follicular cell cytoplasm. This study suggests that the morphological response of thyroid follicular cells to hypophysial portal vascular infusion of TRH occurs rapidly and mimics, both temporally and morphologically, the response observed following systemic administration of exogenous TSH.

Inhibition of dopamine-induced release of growth hormone by thyrotropin-releasing hormone.

The effects of thyrotropin-releasing hormone (TRH) and dopamine (DA) on serum growth hormone (GH) levels were examined in the adolescent male baboon. Intravenously administered DA (40 microgram/kg-min-1 for 20 min) raised serum GH and glucose and lowered serum insulin concentrations but caused no increase in blood pressure. Concomitant intravenous infusion of TRH at 2 doses (96 ng/kg-min-1 and 40 microgram/kg-min-1 for 20 min) blocked the DA-induced increase in serum GH. The relatively low effective doses of TRH used to suppress the DA-induced GH increase suggest an interaction with catecholamines at the hypothalamic and/or pituitary to influence GH release.

Effects of subcutaneous injection and intrahypothalamic infusion of releasing hormones upon lordotic response to repetitive coital stimulation

The effects of luteinizing hormone-releasing hormone (LRH) and thyrotropin-releasing hormone (TRH) upon the lordotic response to repetitive coital stimlation were studied using ovariectomized (OVX) and ovariectomized-adrenalectomized (OVX-ADX) female rats. Both OVX and OVX-ADX rats, pretreated with estrone alone, exhibited a dual behavioral response to repeated coital stimulation. The initial response to short-term stimulation was facilitatory with peak sexual receptivity occurring approximately 120 min following the initial male contact. This initial phase was followed by a depression of sexual receptivity associated with continued coital stimulation. Subcutaneous injection of 500 ng of LRH prior to mating was found to significantly potentiate the initial increases in sexual receptivity and to delay the onset of behavioral depression. The injection of 500 ng of TRH was observed to significantly depress behavioral enhancement due to repetitive coital stimulation. The repetitive coital stimulation model was utilized to localize forebrain areas behaviorally responsive to LRH and TRH. Stainless steel cannulas were implanted into either the medial preoptic area (MPOA), arcuate area (ARC), lateral hypothalamic area (LHA), or cerebral cortex (CC). Cannulated animals, primed with estrone, were tested for sexual receptivity immediately prior to experimental treatment, i.e., the infusion of 0.5 μl of 50 ng of LRH or TRH in 0.9% saline, 0.5 μl of 0.9% saline, or sham infusion. A second mating (postinfusion) test was performed 1.75 hr following infusion. When infused into the MPOA or ARC, LRH significantly enhanced lordotic behavior as compared to values obtained for saline or sham infusions. The infusion of LRH into LHA or CC showed no enhancement beyond the levels observed in control infusions (saline and sham infusions). The infusion of TRH into the MPOA or ARC depressed lordotic enhancement to repeated mating, however, this depression was significant only in ARC. These findings were consistent with previously demonstrated actions of releasing hormones upon neural activity within the MPOA and ARC.

SUPPRESSION BY THYROTROPIN-RELEASING HORMONE (TRH) OF HUMAN GROWTH HORMONE RELEASE INDUCED BY L-DOPA.

Oral administration of L-dopa (600 mg) significantly raised plasma human growth hormone (hGH) in 6 of 7 normal subjects examined. This L-dopa induced hGH release was significantly suppressed by the intravenous infusion of 1 mg of thyrotropin-releasing hormone (TRH). TRH administration alone had no significant effect on plasma hGH. In contrast, plasma human prolactin (hPRL) consistently increased following TRH infusion. L-dopa significantly lowered basal plasma hPRL levels and also significantly blunted TRH-induced hPRL release. These results suggest that TRH plays an inhibitory role in the regulation of hGH secretion in normal subjects, whereas it stimulates hPRL release.

Effect of thyrotropin-releasing hormone (TRH) on plasma glucocorticoids and thyroxine in cattle.

The repeated systemic infusion of TRH (200 mug, twice daily) was effective in repeatedly elevating plasma T4 levels (20-40 min postinfusion) for the 3 experimental days. The post-TRH treatment (saline infusion) exhibited a depression of plasma thyroxine levels, possibly explained by previous high thyroxine levels exerting a suppressive effect on the hypothalamic-pituitary-thyroid axis. A depression of plasma glucocorticoid levels was shown within 1 hr in both experiments after TRH administration. The results indicate that TRH administration (systemic) is effective in temporarily elevating thyroxine levels and simultaneously lowering plasma glucocorticoids in cattle.

Milking, thyrotropin-releasing hormone and prostaglandin induced release of prolactin and growth hormone in cows.

Within 30 min of starting continuous ivy infusion of 333 mug thyrotropin-releasing hormone (TRH)/hr into 12 cows, serum prolactin (PRL) increased more than 10-fold and growth hormone (GH) increased 2.6- to 4-fold above basal concentrations. Constant infusions of 30 mg/hr of prostaglandin F2alpha (PGF2alpha) increased serum PRL and GH to maxima wius infusion of TRH or PGF2alpha, PRL declined throughout the 6- to 13-hr infusion interval although it remained well above preinfusion or saline-infusion control values. Serum GH declined more rapidly than PRL in the face of TRH or PGF2alpha infusions, reaching basal concentrations in one experiment within 1-3 hr. Application of milking stimuli during the 5th hr of TRH infusion caused an additional increase of 23 ng/ml of PRL above the TRH-stimulated concentrations. Similarly, intravenous injection of 5 mg PGF2alpha during the 5th or 12th hr of TRH infusion increased serum PRL an additional 582-682 ng/ml and further increased serum GH 9-91 NG/ML. When 200 mug TRH was injected during the 5th hr of a PGF2alpha infusion, serum PRL increased another 267 ng/ml and GH increased an additional 61 ng/ml. Administration of 10 doses of TRH of 200 mug each in 2 hr did not increase PRL or GH in the serum above that observed when 2.2 mg TRH was infused over a 6-hr period. Collectively, the data suggest that a ceiling exists in cows for secretion of PRL and GH, but this ceiling may be overcome with application of a second heterologous stimulus.