Rise In TSH Research Articles

Alpha-adrenoreceptor blockade with thymoxamine reduces basal thyrotrophin levels but does not influence circadian thyrotrophin changes in man.

We have tested the hypothesis that alpha-adrenergic drive is involved in the nocturnal increase in TSH in man. Seven mildly hypothyroid women (basal TSH levels 5.0-11.0 mU/l), aged 38-60 years, and nine euthyroid women, aged 27-60 years, were studied. Subjects underwent alpha-adrenergic blockade by infusion of thymoxamine (210 micrograms/min from 19.00 to 24.00 h); the same women were used as controls, with saline infused on different nights. Subjects were not allowed to sleep during the study period. A clear evening rise in basal TSH levels was apparent in both normal subjects and patients. Although overall secretion of TSH was slightly decreased in normal subjects (mean +/- S.E.M. area under the curve, 29.93 +/- 0.96 vs 30.71 +/- 0.80 mU/l per h; P less than 0.05), thymoxamine infusion did not produce any major alteration in the gradual rise in TSH levels during the evening (incremental change above baseline +0.96 +/- 0.21 during control infusion and +0.97 +/- 0.27 mU/l during thymoxamine infusion). In mildly hypothyroid patients the TSH changes were exaggerated and alpha-adrenergic blockade caused a reduction in basal TSH levels and a delayed rise in TSH (incremental change above baseline +2.93 +/- 1.42 during control infusion and +2.26 +/- 0.73 mU/l during thymoxamine infusion; P less than 0.02). Overall TSH secretion was significantly decreased by thymoxamine (mean +/- S.E.M. area 106 +/- 2.45 mU/l per h vs 123.32 +/- 3.68 in the control study; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

ADOLESCENT DEPRESSION: NEUROENDOCRINOLOGIC FEATURES

This study was undertaken to determine whether a relationship might be found between the existence of depressive illness in adolescents and alterations in the functional status of the hypothalamic-pituitary-thyroid axis, and was part of a larger study intended to describe diagnostic, biologic, and cognitive features of adolescent depression. Eighteen inpatients were included after being diagnosed with severe depression as determined by two interviewers using two depression inventories and applying DSM III criteria. Thirteen females and five males ranged in age from 14-19 years (mean 15.6 yrs). Each patient was subjected to an overnight dexamethasone suppression test (DST) using a dose of 1 mg and TRH infusion using a dose of 500 mcg. Abnormal responses were defined as any one of the three cortisol levels measured > 5 mcg/dl or a rise in TSH < 7 mcIU/ml. Seven patients showed abnormal responses; two blunted TSH responses (both males), two non-suppression on DST (both females) and both tests abnormal in two males and one female. Baseline TSHs did not differ in the two groups. Clinical features associated with depression did not distinguish between the two groups. In this series, blunted TRH response occurred with frequency equal to non-suppression on the DST.

The pituitary TSH response to TRH is inversely related to the plasma TSH concentration and directly related to the pituitary TSH content during hypothyroidism in the rat.

We studied the effects of degree and duration of hypothyroidism on the pituitary TSH concentration and the pituitary TSH secretory response to TRH. Varying degrees of hypothyroidism were achieved in thyroparathyroidectomized rats (THYREX) by continuous sc infusion of T3 (0.2, 0.3, 0.4, or 0.5 microgram/100 g X day) or T4 (0.6, 1.2, or 1.8 microgram/100 g X day). While T3 was more potent than T4, both resulted in a dose-dependent suppression of the post-thyroidectomy rise in TSH. After 7 or 14 days of severe hypothyroidism (nonreplaced THYREX rats) the pituitary TSH secretory response to TRH (250 ng/100 g body weight, iv) was found to be decreased when compared to that of euthyroid rats. Decreasing the degree of hypothyroidism increased the pituitary secretory response to TRH and the pituitary TSH content. The results indicate that in the hypothyroid rat: severe hypothyroidism results in a blunted pituitary TSH response to TRH through 14 days after thyroidectomy, at 7 and 14 days after thyroidectomy the pituitary TSH response to exogenous TRH is inversely related to the basal plasma TSH concentration, the pituitary TSH concentration increases with the duration of hypothyroidism, the pituitary TSH content is increased by low rates of thyroid hormone replacement, and the pituitary TSH response to exogenous TRH is directly related to the pituitary TSH content.

The effects of chronic intermittent stress on basal and acute stress levels of TSH and GH, and their response to hypothalamic regulatory factors in the rat

The effect of chronic stress on basal and stress-induced alterations of TSH and GH was studied in adult male rats. Chronically stressed rats were subjected 6 days per week for 4 weeks to several acute stressors including saline injections, noise, ether and forced swimming. Each day, one stressor was chosen randomly. Twenty hr after the last stress session, basal levels of TSH were normal or increased, with no altered pituitary response to TRH. In contrast, the TSH rise induced by acute stress was blunted in chronically stressed rats. Chronic stress resulted in lower basal and acute stress levels of GH. These modifications were probably due to changes in the release of hypothalamic regulatory hormones, because no evidence for altered TSH response to TRH, and GH response either to GHRH or to somatostatin, was found. Some abnormal responses of GH to TRH and of TSH to GHRH were observed in chronically stressed rats. These data indicate that this type of chronic stress induced significant changes in basal and acute stress levels of GH and TSH in the rat.

Pulsatile secretion of thyrotropin in man.

To examine pulsatile TSH secretion, serum TSH was determined every 10 min for 24 h in 6 normal subjects and every 15 min in 10 euthyroid patients with underlying thyroid disease. Serum T4, T3, and PRL were simultaneously measured in the 10 patients. Pulsatile TSH secretion was identified in all individuals. There was a highly significant correlation between the mean 24-h TSH concentration and pulse amplitude (P less than 0.001). There was a highly significant inverse correlation between the mean 24-h TSH concentration and pulse frequency (P = 0.002) and between the pulse amplitude and frequency (P = 0.002). The mean serum TSH level at night (1800-0600 h) was significantly higher than that during the day (P less than 0.001) and was associated with increases in pulse amplitude (P = 0.008) and frequency (P = 0.007). TSH pulses did not correlate with serum T4 or T3, but did correlate with serum PRL (P = 0.03) in patients with thyroid disease. We conclude that TSH pulsations can be identified in normal subjects and patients with thyroid disease; elevations in serum TSH levels correlate with an increase in pulse amplitude and a decrease in pulse frequency; the nocturnal rise in serum TSH is associated with increases in both pulse amplitude and frequency; and peripheral serum T4 or T3 concentrations are not closely associated with pulsatile TSH secretion.

Evolution of hypothyroidism in familial goitre due to deiodinase deficiency: report of a family and review of the literature

We studied two sisters who developed large non-toxic goitres in adolescence. Deiodinase deficiency was diagnosed by a rapid thyroid uptake of radioactive iodine (RAI) at 2 hours associated with a marked fall in thyroidal 131I by 24 hours. Serial RAI scans in the second patient documented evolution of the iodine-deficient state. Conservation of intra-thyroidal iodine stores was maintained by avid iodine uptake and failure to release organified 131I. With progressive loss of inorganic iodine, hypothyroidism developed, associated with a rise in serum TSH which further exacerbated the loss of iodine. Treatment with L-thyroxine resulted in an improvement of thyroid function, but normalization was achieved only after small doses of Lugol's iodine were administered. These studies illustrate the variable nature and late onset of an inborn error of thyroid metabolism. This family supports an autosomal recessive mode of inheritance for deiodinase deficiency. We have documented progression from a euthyroid to hypothyroid state resulting from decompensation of iodine conservation mechanisms.

Relationship between thyrotropin and thyroxine changes during recovery from severe hypothyroxinemia of critical illness.

In a prospective study of critically ill hypothyroxinemic we assessed the relationship between serum TSH and T4 during the return of serum T4 to normal during recovery. In this longitudinal study of 60 patients with a variety of critical illnesses, including burns, septicemia, and acute renal failure, serum T4 fell to less than 2.7 micrograms/dl (35 nmol/liter) in 24 patients, of whom 14 survived with return of T4 to normal. A rise in total T4 of more than 1.9 microgram/dl (25 nmol/liter) within 96 h occurred 13 times in 10 patients, while 4 patients had slower increases in T4. All 13 episodes of rapid T4 rise [1.7 +/- 0.8 (+/- SD) to 5.6 +/- 2.1 micrograms/dl] were associated with a marked increase in serum TSH (1.1 +/- 0.8 to 7.0 +/- 5.2 mU/liter), and TSH was transiently above normal during 8 episodes of T4 recovery. In the 6 episodes with sampling less than 6 h apart, the TSH rise consistently preceded the T4 rise. In the 4 patients who received dopamine, TSH and T4 remained low until cessation of therapy. During the TSH rise, only minor changes, which could not account for the increase in total T4, occurred in T4-binding globulin (12.9 +/- 3.3 to 14.8 +/- 3.3 mg/liter), prealbumin (208 +/- 73 to 234 +/- 82 mg/liter), and albumin (28.3 +/- 2.9 to 31.9 +/- 2.9 g/liter). Mean free T4 increased (0.60 +/- 0.34 to 1.45 +/- 0.56 ng/dl), as did total T3 (16 +/- 14 to 76 +/- 44 ng/dl), during the phase of TSH rise, suggesting that the increase in TSH was not simply a consequence of diminished negative feedback due to increased plasma binding. The very close and consistent temporal relationship between TSH and T4 during the recovery phase suggests that TSH may have an essential role in the return of T4 to normal during recovery from critical nonthyroidal illness.

Effect of hypothyroidism on pituitary cytoplasmic concentrations of messenger RNA encoding thyrotrophin β and α subunits, prolactin and growth hormone

Thyroid hormones may directly regulate gene expression in the anterior pituitary. In order to examine this possibility we have studied the effect of hypothyroidism in the rat on pituitary cytoplasmic concentrations of messenger RNA (mRNA) encoding thyrotrophin (TSH) beta and alpha subunits, prolactin and GH. We demonstrated a marked increase in TSH beta and alpha subunit mRNA, accompanied by a decrease in GH mRNA, in the hypothyroid state, changes largely reversed by thyroid hormone replacement. We have thus shown a direct influence of thyroid status on the pretranslational events occurring in pituitary hormone synthesis. The simultaneous rise in cytoplasmic TSH beta and alpha mRNA levels and fall in GH mRNA in hypothyroidism suggests that thyroid status exerts a differential effect on the expression of these genes.

Somatostatin inhibits the dermorphin-stimulated thyrotropin release in man.

We have studied the effect of the intravenous administration of somatostatin (SRIF) on the thyrotropin (TSH) response to intravenous dermorphin (D), a new potent opioid peptide, in 7 healthy men. D significantly increased the serum TSH concentration. SRIF administration prior to, during and after D completely prevented the D-induced rise in serum TSH. These results confirm that D stimulates TSH release in man and that this stimulatory effect can be prevented by SRIF.

Involvement of endogenous somatostatin in the regulation of thyrotroph secretion during acute and chronic changes in diet.

The aim of this study was to investigate the involvement of somatostatin (SRIF) in the thyrotroph adaptation to nutritional changes. For this purpose, we studied the effects of passive immunization with SRIF antiserum (A-SRIF) on the reduced basal TSH secretion in rats starved for 72 h and on the plasma TSH surge following carbohydrate (CHO) refeeding. This latter experiment was performed at two different times of the day in order to elucidate whether SRIF may participate in the regulation of the plasma TSH circadian rhythm. In chronically catheterized rats, we observed that A-SRIF injection induced a similar pattern of plasma TSH rise over a sampling period of 5 1/2 h in both fed and rats starved for 72 h (3-way analysis of variance). In morning experiments, CHO refeeding or A-SRIF injection elicited a significant rise in plasma TSH. The amplitude and duration of the response was proportional to the injected dose. In evening experiments, although basal TSH values were significantly lower than those observed in the morning ones, maximal plasma TSH values after A-SRIF injection were not significantly different. At both times of the day, association of refeeding and A-SRIF injection did not stimulate TSH further than either refeeding alone or A-SRIF alone. In conclusion, our data suggest that SRIF cannot account for the differences in serum TSH levels between fed and starved rats; is not responsible for the diurnal difference in basal serum TSH in starved rats, and seems to be involved in the TSH response to refeeding.

Prolactin and thyrotropin response to blockade of dopamine synthesis by monoiodotyrosine in subjects with postpartum and pathological hyperprolactinemia.

To better understand the state of dopamine (DA) neurotransmission in the tuberoinfundibular DA system (TIDA), monoiodotyrosine (3-iodo-L-tyrosine, MIT), a potent inhibitor of DA synthesis, was acutely administered to 8 normal women, 7 postpartum women, 8 women with pathological hyperprolactinemia and 5 women after successful removal of a prolactinoma. The effects on plasma prolactin (PRL) and thyrotropin (TSH) were compared to those induced in the same subjects by the DA receptor antagonist domperidone (DOM). MIT (1 gpo) and DOM (10 mg iv) induced qualitatively similar hormonal responses, although the PRL- and TSH-releasing effects of DOM were always greater than those of MIT. In control subjects, MIT treatment induced a consistent rise in plasma PRL (peak increment 45.2 +/- 13 ng/ml at 120 min); in the same subjects DOM induced a prompter and higher PRL response, (peak increment 147.8 +/- 26 ng/ml at 30 min). MIT failed to alter plasma TSH levels, while DOM induced a significant rise in plasma TSH. In postpartum women MIT induced a prompter and higher PRL rise than that occurring in controls (peak increment 180.3 +/- 20 ng/ml at 90 min), though also in this instance DOM proved to be a more potent PRL releaser (peak increment 345.7 +/- 88 ng/ml at 30 min) than MIT. MIT was unable to stimulate TSH secretion, while DOM induced a significant rise in plasma TSH. In women with pathological hyperprolactinemia MIT failed to alter baseline PRL levels while DOM slightly increased them (peak increment 14.7 +/- 3 ng/ml at 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Oxytocin attenuates TRH-induced TSH release from rat pituitary cells.

The observation that suckling evokes a modest rise in serum TSH when compared with that of prolactin is inconsistent with the hypothesis that TRH serves as a hypophysiotropic mediator of this response. In the present study we attempted to provide an explanation for this discrepancy by determining whether any of a growing number of putative prolactin releasing factors could alter pituitary responsiveness to TRH. Anterior pituitaries from lactating (day 14) rats were monodispersed with trypsin, cultured for 2 days, and then incubated in the presence of medium alone or medium containing TRH, dopamine, or a combination of these secretagogues. Companion sets of cultures were incubated concurrently with either beta-endorphin, neurotensin, oxytocin, serotonin, vasoactive intestinal polypeptide, or lysine vasopressin. As expected, TRH stimulated and dopamine suppressed prolactin release. None of the substances tested except oxytocin had a significant effect on pituitary cell responsiveness to TRH or dopamine. Oxytocin had no effect on prolactin secretion when tested alone or in combination with TRH and dopamine. TRH alone stimulated TSH release by these cultures, while oxytocin and dopamine were ineffective by themselves. However, TSH secretion by cultures treated simultaneously with TRH and oxytocin could be suppressed to approximately half of that released by cells incubated with TRH alone. These results demonstrate that oxytocin attenuates TRH-induced TSH release by a direct action on pituitary cells without affecting the prolactin response. This selectivity of responsiveness imparted by oxytocin might contribute to the blunted release of TSH after suckling.

Dermorphin, a new opioid peptide, stimulates thyrotropin secretion in normal subjects.

The effect of a recently described, potent opioid peptide, dermorphin (DER), on TSH secretion in euthyroid subjects has been studied. DER infused at a rate of 5.5 micrograms/Kg/min for 30 min induced a significant increase in serum TSH concentration at 60, 90, and 120 min after the infusion was begun. Treatment with naloxone administered 30 min before the DER infusion with a bolus dose of 4 mg, followed by a constant infusion of 1 microgram/Kg/min for 150 min, prevented the rise in serum TSH. Naloxone administered alone did not induce any change in TSH concentration. The present findings suggest that DER has a stimulatory effect on TSH secretion, probably mediated by opioid receptors. These results, however, do not solve the question as to whether opioids have a physiological role in the control of pituitary TSH secretion.

CONGENITAL HYPOTHYROIDISM: THE EFFECT OF STOPPING TREATMENT AT 3 YEARS OF AGE

69 children were detected by a low thyroxine (T4) and/or elevated thyrotropin (TSH) on neonatal screening to have congenital hypothyroidism (CH). Of these, 55 are 3 years of age or older. Thyroid scanning at diagnosis showed 16/55 were athyrotic (A), 21/55 had goiters (G) and 18 with ectopic (E) glands. E were excluded because of the anatomic abnormality. 22 of the remaining 37 showed a secondary rise of TSH to >10 mU/L confirming the diagnosis during the first 3 years. In 15 with continuous TSH suppression, thyroxine was discontinued at age 3 years or more. In the first 6, TSH was measured at 6 weeks: in 5/6 it was >60, in 1 with G-CH, TSH was 7 at 6 weeks and 15 at 8 weeks. Symptoms of hypothyroidism occurred in 4/6. TSH was then measured at 3 weeks and was >60 in the remaining 10. When the TSH was elevated, T4 was 40±39 nmol/L (X̄±SD). In all patients with A-CH or G-CH, the diagnosis was confirmed either by a secondary rise of TSH while on treatment or by a TSH rise at 3-6 weeks after discontinuing therapy. In this group, thyroid screening appears to be 100% specific. Hypothalamic-pituitary responsiveness and hypothyroid symptoms return very rapidly after stopping L-T4 therapy. We recommend TSH measurement 3 weeks after stopping L-T4 in children with CH >3 years in whom confirmation of the initial diagnosis is desirable.

PITUITARY APIASIA IN AN 11 YEAR OLD GIRL: BIOCHEMICAL AND RADIOLOGICAL EVALUATION

An 11 year old girl presented with short stature. Panhypopituitarism was diagnosed and replacement therapy was started with thyroxine, cortisol, and growth hormone treatment, which resulted in catch-up growth. We obtained the following hormonal data: 1) undetectable growth hormone secretion after arginine-insulin (<0.8 ng/ml), 2) no prolactin rise after TRF and chlorpromazine (<2 ng/ml); 3) no TSH rise after TRF (<1.0 μIU/ml), 4) no LH, FSH rise after LRF. When LRF was given 0.025 ug/kg IV every 2 hours for 5 days (Valk, JCEM 53, 184, 1981) LH remained <3.5 m IU/ml and FSH was undetectable. A 5-d ACTH infusion caused a modest rise of plasma cortisol (<0.2 to 8.8 ug/dl), consistent with secondary adrenal insufficiency. Posterior pituitary function and adrenomedullary function were normal. The thyroid responded normally to exogenous TSH. Aldosterone secretion increased upon upright posture and on a low salt diet. Skull radiography showed a shallow sella turcica. Cerebral computed tomography did not identify the pituitary gland and suggested hypoplasia of the right carotid artery. This was confirmed by a a technetium scan of the brain, which showed asymmetric cerebral blood flow. In conclusion, this patient had biochemical and radiological evidence of absence of the pituitary gland. Thus, although she survived without treatment until age 11, she appears to have the syndrome of congenital pituitary aplasia described by Blizzard (J. Ped. 48, 782, 1956). Pituitary vascular insufficiency is a possible cause of this patient's pituitary aplasia.

Direct Adrenergic Stimulation of the Release of Thyrotropin and Its Subunits from the Thyrotropein Vitro*

Adrenergic effects on TSH and subunit secretion were investigated in bovine anterior pituitary monolayer cultures. Epinephrine (E) (10(-6) M) caused a significant increase in TSH, alpha-subunit, and TSH beta release into the medium (P less than 0.001, P less than 0.001, and P less than 0.01, respectively). E, norepinephrine, and phenylephrine, all alpha-adrenergic agonists, caused significant increases in TSH release, with half-maximal effects at 4.3 X 10(-7), 6.8 X 10(-7), and 8.2 X 10(-7) M, respectively. However, isoproterenol, a beta-adrenergic agonist (10(-7)-10(-4) M), did not alter TSH or subunit release. Clonidine, an alpha 2-adrenergic agonist (10(-7)-10(-4) M), had no effect on TSH or subunit secretion; however, coincubation of clonidine (5 X 10(-7) M) with a submaximal concentration of phenylephrine (5 X 10(-7) M) caused a rise in TSH release greater (P less than 0.02) than that seen with P alone. The alpha-adrenergic antagonists phentolamine and fluphenazine completely inhibited (P less than 0.001) the E-induced rise in TSH and subunits. In contrast, the beta-adrenergic antagonists propranolol and metoprolol did not significantly inhibit the stimulation of TSH by E. TSH and subunit secretion is stimulated by adrenergic agonists acting directly on the pituitary, and this is probably mediated via an alpha-adrenergic receptor.

Hypothalamic-pituitary-thyroid axis in acromegaly.

To evaluate the hypothalamic-pituitary-thyroid axis in acromegaly, total and free thyroid hormones and TSH response to TRH were determined in 36 acromegalic patients. In 10 patients, rT3 and thyroxine binding globulin (TBG) were also assayed by radioimmunoassay. In 15 patients the TSH response to TRH was also studied after medical or surgical therapy of the acromegaly. In 34 patients total thyroid hormones were in the normal range whereas two patients had low serum levels of free thyroid hormones. Thirty-two of the acromegalic patients were euthyroid. However, only 43.7% of the euthyroid patients had a normal TSH response to TRH. Nine patients had a reduced TSH rise after TRH, whereas in 4 patients the response was exaggerated and 5 delayed. In all patients studied rT3 and TBG were in the normal range. After medical or surgical therapy of the acromegaly we observed improvement or normalization of the TSH response to TRH. In conclusion, the TSH response to TRH is frequently altered in acromegaly, whereas thyroid function is generally normal. Hypothalamic effects of GH hyperproduction may explain the alterations of TSH secretion in many cases in view of the normalization of TSH secretion after therapy of acromegaly.

The effects of intranasally sprayed synthetic TRH on TSH and on PRL secretion in children.

The effects of intranasally applied TRH on serum TSH and PRL were investigated in ten healthy, prepubertal children. Serum levels of T4, T3, TSH, and PRL were all in the normal range. Synthetic TRH, 500 micrograms, in water was insufflated in one nostril. Intranasal TRH induced a prompt rise of TSH and PRL in all children with peak values at 30 min. TSH: 10.29 +/- 1.24 microU/ml; PRL: 25.12 +/- 3.53 ng/ml (mean +/- SEM). TSH values were still significant raised 120 min after the insufflation (P less than 0.025) whereas the PRL values did not differ significantly. A dose-dependent TSH release following intranasal sprayed TRH was shown. delta TSH and TSH values at 120 min were significantly higher in children receiving greater than 10 micrograms/kg TRH than in children receiving less than 10 micrograms/kg (P less than 0.025; P less than 0.05). Dose dependent differences in PRL release following intranasal TRH were not shown. Any side effects of intranasally applied TRH were not observed. Intranasal insufflation of synthetic TRH seems to be a valuable and harmless tool for the evaluation of pituitary TSH and PRL secretory reserve.

Reciprocal pattern of the TSH and PRL responses to dopamine receptor blockade in women with physiological or pathological hyperprolactinaemia.

The TSH and PRL responses to administration of the two dopamine (DA) receptor antagonists sulpiride and domperidone, were studied in fifteen normoprolactinaemic subjects, twenty-two post-partum women and sixteen subjects with presumptive evidence of (six subjects) or surgically confirmed (ten subjects) prolactinomas. Sulpiride (100 mg i.m.) or domperidone (10 mg i.v.) elicited a slight increase in basal TSH levels in both normoprolactinaemic and post-partum women, but induced a clear-cut TSH rise in subjects with a tumour. Conversely, sulpiride and domperidone strikingly stimulated PRL secretion in normoprolactinaemic and post-partum women, but only slightly enhanced base-line PRL levels in women with prolactinomas. The reason for the reciprocal pattern of TSH and PRL responsiveness to DA receptor blockade of post-partum women and subjects with prolactinomas is presently obscure. Since baseline PRL levels in the two hyperprolactinaemic states overlapped widely, it would appear that hyperprolactinaemia per se is not responsible for such behaviour.

Transient effect of L-5-hydroxytryptophan on pituitary function in men and women.

To further elucidate the role of serotonin in the secretion of pituitary hormones, a loading dose of 0.8 mg/kg for 1 h, following by a maintenance dose of 0.1 mg/kg . h of L-5-hydroxytryptophan (5-HTP) for 23 h were administered iv to five normal men and five normal women. Five additional men received repeated loading doses of 5-HTP 4 and 6 h after the initial one, with or without the maintenance dose. The initial studies demonstrated a significant, but transient, increase in plasma PRL, GH, cortisol (P less than 0.01) and TSH (P less than 0.05) in the five man and a consistent and significant transient increase only in PRL and cortisol in the five women. Plasma LH and FSH values were not affected by 5-HTP administration. The constant administration of 5-HTP revealed a blunting effect on the nocturnal rise of TSH in men. The continuous administration of 5 HTP failed to maintain the rise induced by the loading dose. Individuals receiving additional loading doses of 5-HTP demonstrated a subsequent increase in GH and cortisol, but not in serum PRL. This study suggests that endogenous serotonin may exert its stimulatory effect on pituitary hormone secretion primarily by sporadic release, rather than by continuous secretion.