Radioimmunoassay For Growth Hormone Research Articles

A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective

A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004). ConclusionRare conditions of GH insensitivity caused by GH receptor and postreceptor abnormalities have provided insights into the processes of growth, body composition, and metabolism.

Duration and nature of altered pituitary function in the male rat after a single large dose of estrogen.

The effects of a single large dose (10 and 20 mg) of diethylstilbestrol dipropionate on the pituitary gland of the mature male rat were investigated at intervals up to 312 days. The initial rise in pituitary weight and serum radioimmunoassayable growth hormone and fall in pituitary growth hormone concentration were followed by gradual recovery to normal extending over 5 to 6 months. Testicular weight was diminished until day 136 and adrenal weight was raised until day 114. The early pituitary mitotic activity had subsided to normal by day 69. Pituitary prolactin concentrations as indicated by starch gel electrophoresis were raised on day 28. Enlarged pituitary glands during the period 69 to 140 days also contained increased prolactin concentrations. The individual variations among the rats killed during the latter period included greatly elevated serum growth hormone either with or without increased pituitary weight.

Influence of Fetal Alcohol Exposure on the GABAergic Regulation of Growth Hormone Release in Postnatal Rats

Disruption of the growth hormone (GH) axis by maternal ethanol (ETOH) consumption may contribute to abnormalities in offspring. Interestingly, gamma-aminobutyric acid (GABA) neurotransmission, which is vulnerable to fetal ETOH exposure, also regulates the hypothalamic-pituitary GH axis. This study examines whether GABAergic control of this axis is disrupted by prenatal ETOH exposure. Pregnant dams were fed either rat chow ad libitum or a 36% ETOH diet (by calories), or were pair-fed an isocaloric control diet. Hypothalami and pituitaries from offspring were coperfused, in vitro, with muscimol, a GABA(A) agonist, either alone or in combination with bicuculline, a GABA(A) antagonist. Perfusates were analyzed by radioimmunoassay for GH, somatostatin (SRIF), and GH-releasing factor (GRF). Normal development of GABA regulation was evaluated first in control offspring. Sensitivity to muscimol (measured by percent increase in GH above basal levels) occurred at all ages and generally was greater in male compared to female tissue. Furthermore, the efficacy of bicuculline in depressing muscimol-induced GH secretion increased with age in both sexes. In males, this response correlated with increased SRIF release. In females, releasing factor data were highly variable relative to the percent change and are not presented. Maternal ETOH consumption altered the development of GABAergic regulation of the GH axis in offspring. flowever, because ETOH induced changes in the response of releasing factors to muscimol appear to offset each other, a disruption in GH release was not evident. More apparent was the reduced capacity of bicuculline to reverse muscimol-induced GH release from male tissue. This ETOH effect was evident at 35-days of age and was associated with reduced SRIF release. In female tissue, a reduced bicuculline response was also suggested at 35 days of age. After puberty no response was elicited by muscimol in either tissue from pair-fed or ETOH-exposed female offspring. In summary, fetal ETOH exposure influences the development of GABAergic regulation of the hypothalamic-pituitary GH axis in an age and gender specific manner. Vulnerability of the male axis is expressed by the reduced capacity of bicuculline to depress GH release and altered releasing factor sensitivity to GABA(A)-receptor stimulation or inhibition. There is also some suggestion that the female axis is less sensitive to bicuculline during early puberty, and, unlike the male, is insensitive to both muscimol and bicuculline after puberty. The latter, however, may be attributable to stress or nutritional deprivation, rather than to the direct effect of prenatal ETOH.

Enhancement by Proopiomelanocortin-Derived Peptides of Growth Hormone and Prolactin Secretion by Bullfrog Pituitary Cells

Corticotrophs in the bullfrog (Rana catesbeiana) are situated mainly in the rostral region of the anterior lobe of the pituitary gland, which receives its blood supply primarily from the portal vessel. On the assumption that the proopiomelanocortin (POMC)-derived peptides released into the pituitary circulation may influence the function of other pituitary cells situated downstream, the effects of three POMC-derived peptides, namely, N-terminal peptide of POMC (NPP), adrenocorticotropic hormone (ACTH), and joining peptide (JP), on the secretion of growth hormone (GH) and prolactin (PRL) by bullfrog dispersed anterior pituitary cells were examined. NPP and ACTH, but not JP, stimulated the release of GH and PRL in a concentration-dependent manner. It was also found that ACTH1–17, but not α-melanocyte-stimulating hormone, was effective in enhancing GH and PRL release. A marked difference between the response to NPP and ACTH and the response to thyrotropin-releasing hormone employed as a reference secretagogue in terms of the time required for stimulating the release of GH and PRL was noted. Northern blot analysis of GH and PRL mRNA levels and radioimmunoassay for GH and PRL in the cultured cells revealed that ACTH increases the syntheses of both pituitary hormones as well. The possibility that NPP and ACTH act on neighboring cells to maintain their overall secretory function is discussed.

Photoperiod Regulation of Plasma Growth Hormone Levels during Parr-Smolt Transformation of Atlantic Salmon: Implications for Hypoosmoregulatory Ability and Growth

The influence of photoperiod on plasma growth hormone (GH) levels during parr smolt transformation was studied in Atlantic salmon, using a specific salmon GH radioimmunoassay; in addition, the impact of endogenous changes in GH levels on hypoosmoregulatory ability and growth was assessed using seawater challenge tests and measurements of growth rates. Groups of fish were kept on simulated natural photoperiod or continuous light, and subgroups were subjected to reciprocal transfers between these two light regimes at different times. For Atlantic salmon on simulated natural photoperiod, GH levels increased during the parr-smolt transformation, from 0.6 ng ml-1 in January-March to 6.6 ng ml-1 in June, while the corresponding change in fish on continuous light was from 0.4 to 1.0 ng ml-1. The study demonstrates that photoperiod is a major zeitgeber for the increased GH levels during the parr-smolt transformation of Atlantic salmon. The data further support the view that exposure to continuous light into fall and winter causes a "free running" of an endogenous rhythm governing smolting and a subsequent phase-delay of the parr-smolt transformation-related increase in plasma GH levels. A strong positive nonlinear correlation was found between specific growth rate and GH levels, with growth rate increasing rapidly with increasing GH levels up to 2-3 ng ml-1 at which point near maximal growth rate is reached. revealing that relatively small increases in GH levels may be of great importance for an increased specific growth rate. A positive nonlinear correlation was also found between GH and hypoosmoregulatory ability, leading to the conclusion that a regime of continuous light has adverse effects on seawater tolerance and that a period of short daylength is necessary for the normal smolt-related physiological improvement in seawater adaptability.

Defining growth hormone deficiency in adults

The absence of a distinct clinical syndrome calls for a strategy to reliably identify patients with hyposomatotropism. However, there is no consensus as to the most appropriate method of defining growth hormone (GH) deficiency in adults. Since GH secretion falls with senescence and is also reduced by obesity, both of these factors must be controlled for in such an evaluation. We have investigated the relative diagnostic merits of measuring (1) peak GH response to insulin-induced hypoglycemia (ITT), (2) mean 24-hour GH concentration derived from 20-minute sampling (IGHC), (3) serum IGF-I levels, and (4) serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) levels. These tests were undertaken in 23 patients considered GH-deficient from extensive organic pituitary disease and in 35-sex-matched normal subjects of similar age and body mass index. The ITT was the only test capable of distinguishing patients with organic GH deficiency from matched normal subjects. The sensitivity of the GH radioimmunoassay (0.2 ng/mL) limited the utility of IGHC measurements, since many subjects from both groups had undetectable values. Using a GH assay with a 100-fold greater sensitivity, we found a better but still incomplete separation of values between the two groups. There was a significant overlap of IGF-I and IGFBP-3 values, with only a third of GH-deficient subjects having low IGF-I values. The limitation of IGF-I has been confirmed by others, although its sensitivity as a diagnostic test is greater in young adults. We conclude that organic GH deficiency in adults can be reliably diagnosed by the ITT. IGF-I and IGFBP-3 measurements are unreliable, because these levels may be normal in GH deficiency.

Purification, partial characterization, and heterologous radioimmunoassay of growth hormone (cGH) in red deer

Red deer growth hormone (cGH; 3.3 mg) was purified from an aqueous extract of seven pituitary glands (4.01 g wet weight) by preparative gel filtration on Sephadex G-100, gel filtration on Sephadex G-100 SF, and anion exchange chromatography on DEAE-Sepharose CL-6B. Purified cGH gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight under reducing conditions of 20,000 Da and gave a single peak on reverse-phase high-performance liquid chromatography. N-Terminal amino acid determination of 42 residues gave a sequence identical with those published for bovine and ovine GH. In a radioreceptor assay based on binding of iodinated recombinant bovine GH ( rbGH) to liver microsomes prepared from a pregnant ewe, cGH was equipotent with an ovine GH (oGH) standard. In an oGH radioimmunoassay, cGH diluted in parallel with oGH and rbGH. Using this assay plasma GH concentrations were determined in adult nonpregnant red deer hinds over a 12-month period. There was a significant seasonality in plasma GH concentrations with concentrations consistently low between mid-May and mid-September. This is the period when voluntary food intake and liveweight gain are greatest. It is suggested that in the presence of low plasma GH concentrations nutrients may be diverted toward lipogenesis and hence promote fat deposition.

Morphological effects of somatostatin on rat somatotrophs previously activated by growth hormone-releasing factor

Correlative morphological and physiological analysis was carried out in order to clarify the role of somatostatin in the inhibition of the secretion of growth hormone (GH) from somatotrophs of the rat anterior pituitary gland in vivo. Transmission electron microscopy combined with immunogold labelling showed an increased number of exocytotic GH-containing secretory granules in somatotrophs fixed between 2 and 10 min after injection of GH-releasing factor (GRF). Injection of GRF also induced the appearance of immunopositive material in cisternae of the Golgi apparatus, many coated vesicles and multivesicular bodies. Microtubules were observed more frequently throughout the cytoplasm, particularly in and near the Golgi region. At 2 and 10 min after injection of somatostatin (SRIF), both the number of exocytotic figures in the somatotrophs previously stimulated by GRF and the amount of radioimmunoassayable GH in the plasma were clearly decreased. Undulation of the plasma membrane (PM) induced by GRF rapidly disappeared, and the number of granules just beneath the plasma membrane was significantly reduced. After injection of SRIF, parallel bundles of microfilaments were often observed in the space between the granules and the plasma membrane. SRIF did not cause a noticeable decrease in the amount of immunopositive material, coated vesicles and multivesicular bodies in the Golgi areas or any significant changes in the distribution of microtubules. SRIF therefore appears to inhibit hormone release mainly at the level of the plasma membrane, probably through changes in the distribution of microfilaments.

GROWTH WITHOUT GROWTH HORMONE: THE "INVISIBLE" GH SYNDROME

Growth hormone (GH) deficiency, diagnosed by radioimmunoassay (RIA) measurements of GH in blood after provocation or in continuous 24 h samples of venous blood, is usually associated with growth failure. 4 non-obese boys have been identified who had normal linear growth despite apparent GH deficiency by standard RIA. All 4 patients had normal GH concentrations as measured with an IM-9 cell radioreceptor assay (RRA). The RRA/RIA ratio of the 4 patients significantly exceeded that of controls. Thus, these patients secrete a molecule with normal GH receptor binding and bioactivity which is "invisible" to the standard GH RIA. This variant GH is possibly expressed from the human GH-V gene or a mutant allele.

Quantitation of urinary growth hormone in children with normal and abnormal growth.

Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean +/- SEM per kg body weight) in group 1 (0.27 +/- 0.02 ng/kg) was significantly greater than group 2 (0.08 +/- 0.02 ng/kg) or group 3 (0.17 +/- 0.02 ng/kg, p less than 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 +/- 0.07 versus 0.12 +/- 0.02 ng/kg, p less than 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.

Development and validation of a salmon growth hormone radioimmunoassay

A highly specific and sensitive radioimmunoassay (RIA) for the measurement of plasma and pituitary growth hormone (GH) levels in salmonid fishes was developed using an antiserum raised in rabbit against chum salmon ( Oncorhynchus keta) GH (sGH). Pituitary extracts and plasma from chum, coho, masu, and amago salmon, and from rainbow trout and Japanese charr, all exhibited displacement curves parallel to the sGH standard. Samples from the eel, carp, goldfish, and tilapia, as well as plasma from hypophysectomized chum salmon and rainbow trout, all showed negligible cross-reactivity. None of the mammalian or teleostean GH or prolactin preparations tested cross-reacted with the antibody in the assay system. RIA sensitivity was 0.6 ng sGH/ml of plasma when 100 μl of plasma was employed. Intra- and interassay coefficients of variation were 3.9 and 4.1%, respectively. Plasma GH levels of the mature chum salmon caught in Otsuchi Bay were highly variable, especially in females (20.2 ± 8.2 ng/ml) as compared with males (16.0 ± 1.1 ng/ml), and there was no significant change after transfer to fresh water. Whereas there was no change in plasma GH levels in males kept in seawater, the levels in females increased with time in close correlation with the increase in plasma chloride.

Somatic growth in hypophysectomized pituitary-homografted rats is promoted by prolactin.

Hypophysectomized male rats bearing a homograft of two adenopituitaries under the kidney capsule showed a significant increase in b.wt as compared to hypophysectomized non-homografted animals. Radioimmunoassay of growth hormone (GH), ACTH, alpha-MSH, beta-endorphin and prolactin (PRL) revealed that only the latter was highly increased in the plasma of hypophysectomized homografted rats. These animals showed also increased levels of plasma corticosterone. However, daily injection of corticosterone failed to promote somatic growth in hypophysectomized non-homografted rats. These results suggest that PRL, and not other hormonal factors, promotes somatic growth in hypophysectomized homografted rats, and stress the concept that only PRL is secreted in significant amounts by pituitary homografts.

Recombinant-derived chicken growth hormone used for radioimmunoassay.

The use of recombinant-derived chicken growth hormone (rcGH) in an avian growth hormone (GH) radioimmunoassay (RIA) procedure is described. Antiserum to turkey GH bound 125I-labeled rcGH, and unlabeled rcGH or turkey GH displaced binding in a dose-related manner. The dose-response curves of sera and pituitary extract from chickens and turkeys were parallel to the rcGH standard curve. Sera from hypophysectomized (hypox) chickens and turkeys produced no dose-response and did not inhibit binding of labeled rcGH. Recovery of rcGH added to hypox sera was quantitative. Modification of the homologous turkey GH RIA protocol of Proudman and Wentworth (1) to use rcGH made possible either an increase in assay sensitivity or a 3-day reduction in incubation time.

Ultrastructure of pituitary somatotrophs of male rats during liver carcinogenesis by 3′-methyl-4-dimethylaminoazobenzene

Somatotrophs of male Wistar rats fed a carcinogenic dose of the potent hepatocarcinogen 3'methyl-4-dimethylaminoazobenzene-(3'MeDAB) in a complete diet for up to 21 weeks, showed ultrastructural changes within one week of the start of the experiment. Morphometric analysis showed that the area of the somatotrophs occupied by hormone storage granules was reduced significantly at all stages up to 21 weeks, when the experiment was terminated. The cell area occupied by rough endoplasmic reticulum (RER) was significantly increased after three weeks and RER surface density increased after eight weeks, whilst granule size was reduced after four weeks. Pituitary content of radioimmunoassayable growth hormone (RIA-GH) was also lower in treated rats than in controls, from one week after the start of the experiment, but only significantly so at eight and twelve weeks, owing to large standard errors. Serum levels of RIA-GH were similarly lower in 3'MeDAB treated rats than in controls. Withdrawal of 3'MeDAB diet after twelve weeks treatment permitted partial recovery of some cell organelles, in that the content of hormone storage granules increased and the area of the RER decreased compared to rats fed 3'MeDAB continuously. There was also a partial, but non-significant, increase in pituitary RIA-GH. The pituitaries of rats pair-fed 3'MeDAB diet for 15 weeks contained significantly less RIA-GH than matched controls. These results suggest that 3'MeDAB, or its metabolites, may react with pituitary somatotrophs and impair their ability to synthesise and secrete hormone.

Development and validation of a carp growth hormone radioimmunoassay

Purified growth hormone (GH), isolated from pituitary glands of the common carp ( Cyprinus carpio), was shown to have biochemical and immunological properties in common with other teleost GH preparations. Intraperitoneal injections of the carp GH, at a dose of 1 μg/g body wt, resulted in significant increases in body weight in goldfish. In addition, the carp GH was used to prepare an antiserum for the development of a radioimmunoassay (RIA). The displacement curves for serum from goldfish with an intact pituitary gland were parallel to that of the purified cGH in this RIA. In contrasts serial dilutions of serum from hypophysectomized goldfish, and purified goldfish prolactin and carp gonadotropin did not have significant cross reaction. The present study strongly suggests that this RIA is suitable for the measurement of circulating GH levels in the goldfish.

Inappropriately low serum GH in an acromegalic: Lysosomal involvement in intracellular hormone degradation

A patient with galactorrhea, amenorrhea and severe acromegaly was found to have a large pituitary adenoma. In view of the severity of the disease the serum growth hormone (GH) level (22.5 mlU/liter) was considered inappropriately low. Tissue from the adenoma was obtained during successful treatment with interstitial irradiation ( 90Yttrium). Trypsindispersed biopsy cells in culture for 12 days secreted low amounts of GH compared to the same number of adenoma cells from 5 other unselected acromegalics or a normal pituitary. No other hormones were secreted in culture. Immunocytochemical staining was positive only with GH antisera but showed low intracellular content. This was confirmed by direct analysis of the tumor tissue which showed the GH content to be only 20% of that found in 5 normal pituitaries and 4% of that found in 8 other adenomas from acromegalics. Electron microscopy showed a striking appearance, with GH secretory granules that were sparse in number, smaller than usual, and in the main arranged around numerous intracellular profiles with double membranes and low electron density that were tentatively identified as autophagic vacuoles (secondary lysosomes). Subcellular fractionation showed the distribution of the radioimmunoassayable GH in the gradient to be coincident with the peak of the lysosomes whereas in 2 other acromegalics the GH peak was clearly separated from the lysosomes. We conclude that the simultaneous appearance in our patient of a relatively low serum GH together with a large tumor and severe acromegaly can be explained biochemically by the striking finding of crinophagy - disposal of hormone secretory granules within the somatotroph cells themselves.

Immunochemical Determination of Pituitary Growth Hormone Separated by Polyacrylamide Disc Gel Electrophoresis in Normal and Dwarf Chickens

Chicken pituitary growth hormone (GH) was determined by a heterologous radioimmunoassay for rat GH following separation of the hormone by polyacrylamide disc gel electrophoresis. The GH was concentrated in the slowest migrating protein band, called either TSH (thyroid stimulating hormone) or SP (slow-moving protein), which has been proven to have somatotropic activity in the toad. The distribution pattern of radioimmunoassayable GH was the same in the normal and dwarf chickens of both sexes.

Roth: diabetes and receptors

the traditional treatments of diabetes, laboratory studies were uncovering the reason. A radioimmunoassay for insulin—the first such assay ever developed—was used by Solomon A. Berson, MD, Rosalyn S. Yalow, PhD, in the early 1960s to measure circulating levels of insulin in diabetics. Their data showed that only 20% to 30% of diabetics are insulin-deficient, Roth recalls, and that in the majority of cases, diabetes is not an insulin-deficiency disease. These findings came at the time that Roth was finishing his internship residency at Washington University. Subsequently, he was awarded a fellowship by the American Diabetes Association to study in Berson Yalow's laboratory, where he worked on a radioimmunoassay for growth hormone. (Roth has decided views on the role of a physician going into basic research. You start out with a severe disadvantage in formal scientific training. But you have the advantage that

Cure of acromegaly by operative removal of an islet cell tumor of the pancreas

We studied a 30 year old woman in whom acromegaly was cured by operative removal of a large cystic beta cell adenoma of the pancreas. We detected substantial amounts of immunoreactive human growth hormone (hGH) -like activity in a tumor tissue extract. Extracts of the tumor and a normal human pituitary gland eluted from a Sephadex ® G-75 column in two identical peaks. Serial dilutions of the tumor extract displaced radioactive 125I hGH parallel to a standard curve. Surprisingly, an extract of a normal human pancreas contained large amounts of hGH-like activity and gave results similar to those of the tumor extract on gel chromatography and on serial dilution displacement in the growth hormone immunoassay. Paper electrophoretic studies of 125I hGH after incubation with normal pancreatic and tumor extracts with and without enzyme inhibitors suggested that pancreatic proteolytic enzymes damaged the 125I hGH used in growth hormone radioimmunoassay and produced a false detection of hGH.

Hypophysial portal vascular infusion of TRH in the rat: An ultrastructural and radioimmunoassay study

The hypophysial portal vessels and anterior pituitary gland of adult male Wistar rats were exposed surgically. A hypophysial portal vessel was cannulated and infused for one minute with saline or thyrotrophin (TRH). Anterior pituitary glands were collected at 1,5,15,30 or 60 minutes after cessation of infusion, for light and electron microscopic examination. Before and immediately after cannulation of a portal vessel, a 1-ml sample of blood was collected at 1,5,15,30, or 60 minutes, from the femoral vein for radioimmunoassay (RIA) of growth hormone. Thyrotrophs from anterior pituitary glands of rats infused with TRH displayed emiocytic activity at all time-periods studied. Rough endoplasmic reticular (RER) cisternae were dilated at 15 minutes following infusion and remained dilated at 30 and 60 minutes. TRH was observed to stimulate emiocytic activity in most pituitary cell-types. Extensive dilations of RER cisternae were also observed in mammotrophs and gonadotrophs, but were not observed in somatotrophs or adrenocorticotrophs. The demonstration that thyrotrophs, mammotrophs, somatotrophs, and gonadotrophs respond to TRH suggests that some common features may be shared by these cells. Preliminary analysis of the RIA data show that TRH was potent in elevating radioimmunoassayable growth hormone levels. Significant increases (p less than 0.02) in plasma GH levels were present at the earlier time periods studied (1,5, and 15 minutes) following the infusion of TRH, but no at 30 or 60 minutes. These findings provide additional support for the non-specific action of TRH upon hte various adenohypophysial cell types, and demonstrate that TRH stimulates these cells by a direct action on the adenohypophysis.