Elevated Plasma GH Levels Research Articles

Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up.

The biochemical diagnosis of acromegaly is conventionally based on elevated plasma GH levels that fail to suppress after an oral glucose load. We studied 16 newly diagnosed patients with acromegaly with normal mean plasma GH but elevated age and gender-adjusted plasma IGF-I concentrations (476 +/- 29 microg/liter, mean +/- SE). Plasma GH was sampled every 10 min for 24 h, and an oral glucose tolerance test was performed. The control group included 46 healthy subjects. All patients had 24-h mean GH values that overlapped with those of the healthy controls. Mean plasma GH was less than 2.5 microg/liter in 12 patients. Patients had higher 24-h nadir GH values than healthy controls (P < 0.001). During the oral glucose tolerance test, nadir plasma GH was less than 1 micro g/liter in eight patients. Plasma IGF-I normalized in 11 of 14 patients after transsphenoidal surgery. Four patients with normal IGF-I after transsphenoidal surgery were restudied. Mean and nadir GH decreased in all of them. In our experience in many patients with acromegaly, the diagnosis could be missed if only the existing GH-based criteria are used. Revised GH criteria in combination with plasma IGF-I should be used for the diagnosis and follow-up of acromegaly.

Eficácia da cabergolina no tratamento da acromegalia

Avaliamos o efeito da cabergolina (1 a 1,5mg duas vezes por semana, por 2 a 4 meses) em 9 pacientes acromegálicos em um estudo prospectivo, não andomizado. Normalização dos níveis de GH e IGF-1 ocorreu em 3 dos 9 pacientes avaliados (33%), em 3 dos 5 pacientes (60%) com tumores co-secretores de GH e prolactina, mas em nenhum daqueles sem hiperprolactinemia associada. As melhores respostas terapêuticas aconteceram nos pacientes cujos níveis pré-tratamento de GH e IGF-1 eram &lt;20ng/mL e &lt;750ng/mL, respectivamente. Nossos achados sugerem que a cabergolina representa uma eficaz opção terapêutica para acromegálicos com adenomas co-secretores de GH e prolactina, sobretudo na presença de moderada elevação dos níveis séricos de GH e IGF-1 .

Deficits in female reproductive function in GH-R-KO mice; role of IGF-I.

Mice homozygous for targeted disruption of the GH receptor/GH binding protein gene (GH-R-KO mice; -/-) exhibit reduced plasma IGF-I levels, elevated plasma GH levels, and dwarf phenotype. Although most GH-R-KO mice are fertile, age at first conception is greatly delayed in -/- x -/- matings. Here we report that the age of vaginal opening is significantly delayed in GH-R-KO vs. normal mice, but it can be advanced by treatment with recombinant human (rh)IGF-I. In pregnant GH-R-KO females, fetal size is reduced and pregnancy is prolonged while placental weight is, unexpectedly, increased. Alterations in fetal and placental weight are related to maternal rather than fetal genotype. Moreover, litter size and body weight of newborn pups are significantly reduced in GH-R-KO vs. normal females. Reduction in litter size reflects both dam and sire effects. We conclude that GH resistance and consequent reduction in peripheral IGF-I levels is associated with delay of female puberty, alterations in fetal and placental growth, delay of parturition, and reduced litter size.

Gonadotrophs but not somatotrophs carry gonadotrophin-releasing hormone receptors: receptor localisation, intracellular calcium, and gonadotrophin and GH release.

Gonadotrophs are the primary target cells for GnRH in the pituitary. However, during a limited period of neonatal life in the rat, lactotrophs and somatotrophs respond to GnRH as well. Also, in the adults of a number of teleost fishes (e.g. carp, goldfish, and tilapia but not trout), GnRH is a potent GH secretagogue. In studying hypophysiotrophic actions of the two forms of GnRH present in the African catfish (Clarias gariepinus), chicken GnRH-II ([His5,Trp7,Tyr8]GnRH; cGnRH-II) and catfish GnRH ([His5,Asn8]GnRH; cfGnRH), we have investigated the effects of GnRH on catfish gonadotrophs and somatotrophs. GnRH binding was examined by incubating dispersed pituitary cells attached to coverslips with 125I-labelled [D-Arg6,Trp7,Leu8,Pro9-Net]GnRH (sGnRHa), a salmon GnRH analogue with high affinity for the GnRH receptor. Following fixation and immunohistochemistry using antisera against catfish LH and GH, 125I-labelled sGnRHa was localised autoradiographically and silver grains were quantified on gonadotrophs and somatotrophs. Specific binding of 125I-labelled sGnRHa was restricted to gonadotrophs. Both cfGnRH and cGnRH-II dose-dependently inhibited 125I-labelled sGnRHa binding to gonadotrophs. To substantiate the localisation of functional GnRH receptors, the effects of cfGnRH and cGnRH-II on the cytosolic free calcium concentration ([Ca2+]i) were examined in Fura-2-loaded somatotrophs and gonadotrophs. GnRH-induced increases in [Ca2+]i appeared to be confined to gonadotrophs, in which both endogenous GnRHs caused a single and transient increase in [Ca2+]i. The amplitude of this [Ca2+]i transient depended on the GnRH dose and correlated well with the GnRHs' effect on LH release. In vivo experiments demonstrated that GnRH treatments which markedly elevated plasma LH levels had no effect on plasma GH levels, while a dopamine agonist (apomorphine) significantly elevated plasma GH levels. We conclude that the two endogenous forms of GnRH in the African catfish are not directly involved in the regulation of the release of GH, suggesting that GnRHs cannot be considered as GH secretagogues in teleosts in general.

Control of growth hormone secretion from porcine fetal and neonatal pituitary tissue in vitro by growth hormone-releasing hormone, somatostatin, and insulin-like growth factor.

The physiological mechanism underlying the enormously elevated fetal plasma GH concentrations in mammalian species is not well understood. We postulated that a decreased sensitivity to the inhibitory effects of somatostatin (SRIH) and insulin-like growth factor-1 (IGF-1) at the pituitary level during porcine fetal life might be one factor in the high plasma GH levels. Therefore, the acute effects of GH-releasing hormone (GHRH), SRIH, and IGF-1 on GH release from the porcine anterior pituitary (AP) were studied using a perifusion system. AP tissue pieces from male and female fetuses (95 days postcoitum) and piglets (10-12 days postpartum) were perifused (at least 6 replicates per treatment and sex) at a rate of 0.1 ml/min and fractions were collected at 10-min intervals. Tissue was subjected to various treatments in random order: a 10-min GHRH pulse (1 nM) with or without concomitant 40-min exposure to SRIH (1, 10 or 100 nM) or IGF-1 (1 or 10 nM) or exposure to SRIH or IGF-1 alone (10 nM each). None of the treatments revealed sex differences, therefore data from males and females were pooled. Exposure to GHRH resulted in a rapid stimulatory GH response both in fetuses (from 61.1 +/- 4.1 to 125.6 +/- 4.7 ng GH.80 min-1.mg-1 AP, p < 0.05) and neonates (from 58.1 +/- 5.3 to 104.6 +/- 4.5 ng GH.80 min-1.mg-1 AP, p < 0.05). Exposure to the lowest dose of SRIH or IGF-1 (1 nM) during GHRH pulse inhibited (p < 0.05) the GH response to GHRH in neonates (74.3 +/- 3.9 and 72.5 +/- 6.3 ng GH.80 min-1.mg-1 AP, respectively), but not in fetuses (115.9 +/- 5.8 and 118.7 +/- 5.4 ng GH.80 min-1.mg-1 AP, respectively). When high doses of SRIH (10 or 100 nM) or IGF-1 (10 nM) were used, the GHRH-induced GH release was totally blocked in neonates (p < 0.05). However, in fetuses the GH response was inhibited only during the first 40 min after GHRH, and a rebound or delay effect occurred during the next 40 min. Irrespective of these general findings, some individual profiles from fetuses (4 profiles) showed that 1 nM SRIH or IGF-1 could inhibit GHRH-induced GH secretion. In contrast, individual profiles from neonates indicated that high doses of SRIH (7 profiles) or IGF-1 (5 profiles) were unable to block GH release stimulated by GHRH. On the other hand, a paradoxical stimulation of GH was observed during treatment with SRIH alone in three individual profiles from fetuses. These data confirm our hypothesis that the highly elevated plasma GH levels in the porcine fetus in vivo (compared to neonates) may be explained, at least in part, by a decreased sensitivity to the inhibitory effects of SRIH and IGF-1 at the pituitary level during fetal life. Results from some profiles indicated individual variations in the maturation of the GH control system, and moreover, even a 'paradoxical' enhancement of GH release in some fetal GH profiles.

The accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels

Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is GH dependent, and that very early changes in plasma GH and/or IGF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 μg/kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasma GH profiles were determined by RIA. Renal IGF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54±7 ng/mlvs 30±5 (1-6 h); 23±10 (9-15 h); and 13±3 ng/ml (24-30 h post-STZ);P<0.05 for all STZ groupsvs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (GRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic GRF-AN administration reduced plasma IGF-I levels significantly to 63% of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467±49 ng IGF-I/g KW in control salinevs 778±100 in saline/STZ and 705±87 ng IGF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in GH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation.

Expression of insulin-like growth factor I in normally and abnormally developing coho salmon (Oncorhynchus kisutch).

Changes in levels of insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) in tissues of normally and abnormally growing (stunted) juvenile coho salmon in seawater were studied. Profiles of hepatic IGF-I mRNA levels were compared with changes in growth and plasma concentrations of GH and insulin. In normally growing fish, IGF-I mRNA levels, as measured by solution hybridization-RNase protection assay, showed that hepatic IGF-I mRNA levels of yearling salmon were highest in May and June. Increased hepatic IGF-I mRNA levels followed increases in both plasma GH and insulin. Levels of hepatic IGF-I mRNA decreased in July, after a sharp decline in plasma GH in June, and remained low until the following spring. The growth rate for normal fish also decreased during fall and winter. After increases in plasma GH and insulin, which peaked in late February, hepatic IGF-I mRNA levels increased rapidly and reached a second peak in April. Increases in plasma GH and hepatic IGF-I mRNA observed in the second year were smaller and occurred earlier than in the first spring in seawater. Growth retardation (stunting) resulted from the premature transfer of cultured fish to seawater. Compared with normally growing fish, these stunted salmon had significantly higher levels of plasma GH but lower levels of plasma insulin. Hepatic IGF-I mRNA levels in stunted salmon were significantly lower, despite elevated plasma GH levels. These results indicate that hepatic levels of IGF-I mRNA in juvenile coho salmon increase in springtime, after an increase in plasma GH and insulin. These seasonal increases in GH and IGF-I precede the rapid growth period coinciding with the springtime increases in temperature and photoperiod and may therefore be associated with these environmental cues. The elevated plasma GH and reduced hepatic IGF-I mRNA levels observed in growth-retarded salmon suggested that stunted salmon may be GH resistant. Hepatic GH resistance and diminished IGF-I production may be the central endocrine defects leading to growth retardation in stunted salmon.

Progestin-induced growth hormone excess in the dog originates in the mammary gland.

In the dog endogenous progesterone and synthetic progestins may incite overproduction of GH, resulting in acromegaly and insulin resistance. This progrestin-induced excessive GH secretion is characterized by disappearance of the pulsatile secretion pattern and insensitivity to both stimulation with GHRH and inhibition with a somatostatin analog. This progestin-induced GH hypersecretion is not associated with neoplastic transformation at the pituitary level. These observations were the impetus for a search of a possible extrapituitary site of GH production. In four ovariohysterectomized dogs elevated plasma GH levels (46.5 +/- 7.7 micrograms/liter; mean +/- SEM) were induced by administration of synthetic progestins. In these dogs hypophysectomy did not led to a significant decrease in plasma GH levels. Analysis of the GH content of various tissue homogenates revealed that the highest GH immunoreactivity was found in extracts of the mammary gland. Ectopic production of GH in the mammary gland was confirmed by lowering of plasma GH concentration to values within the reference range within 2 h after complete mammectomy in two dogs with progestin-induced elevations of plasma GH levels. In one of these dogs the arterial and elevations of plasma GH levels. In one of these dogs the arterial and venous GH concentrations across the mammary gland were measured and an arterio-venous GH gradient was demonstrated. Displacement studies in the RIA and analysis by reversed-phase HPLC revealed that mammary-derived GH is highly similar to pituitary-derived GH. Immuno-histochemical staining revealed that GH immunoreactivity was localized in focal areas of hyperplastic ductular epithelium. In mammary tissue of healthy untreated female dogs no GH immunoreactivity was found. It is concluded that treatment of dogs with synthetic progestins can induce the overproduction of GH in the mammary gland. This GH is biologically active, highly similar to pituitary derived GH, and originates from foci of hyperplastic ductular epithelium of the mammary gland.

Systemic growth hormone does not affect human sleep.

Subsequent to sleep onset, GH concentrations increase markedly, suggesting a stimulatory influence of sleep on GH secretion. However, results have been inconsistent as to whether GH conversely exerts a significant influence on sleep. Hence, the effects of exogenous administration of GH and of GH secretion stimulated by GH-releasing hormone (GHRH) on sleep were reexamined in 3 experiments in healthy male volunteers. In Exp I, 12 men participated on 3 experimental nights, receiving a constant iv infusion of 5 IU GH (between 2100-0700 h), an im bolus injection of 5 IU GH at 2100 h, and placebo. In Exp II, the effects of a short iv infusion of a high dose of 48 IU GH (between 2345-2315 h) on sleep were evaluated in 3 men. In Exp III, the effects of continuous infusion of 30 micrograms/h GHRH (between 2200-0700 h) on sleep were compared to the placebo condition in 10 men. Experiments were double blind, within-subject, cross-over comparisons and included an adaptation night before experimental nights. On all nights, the subjects went to bed at 2300 h and were awakened at 0700 h. Administration of GH elevated plasma GH and somatomedin-C levels throughout the night (P < 0.005). Neither im administration of 5 IU GH nor iv administration of 5 and 48 IU GH had any effect on the total sleep time or the time spent in different sleep stages during the whole night or in the first and second halves of sleep time. Infusion of GHRH increased nocturnal GH secretion (P < 0.005), but the episodic pattern of GH secretion was maintained. However, sleep remained unchanged during GHRH infusion. From these results we conclude that in healthy man, systemic GH has no physiological role for sleep regulation.

Radioreceptor Assay for growth hormone in coho salmon (Oncorhynchus kisutch) and its application to the study of stunting

Binding sites for native chum salmon growth hormone (sGH) in coho salmon (Oncorhynchus kisutch) hepatic membranes were analyzed by radioreceptor assay. Displaceable (specific) binding represented up to 25% of total radiolabeled sGH added. Binding was dependent on buffer pH and membrane protein concentration, and was complete by 24 hours at 15 degrees C. Specific binding was greatest in liver membranes, and was also detected in muscle, ovary, gill, kidney, and brain. Scatchard analyses indicated a single class of hepatic binding sites that were specific for sGH. In stunts, abnormal seawater salmon with elevated plasma GH levels and inhibited growth, specific binding of sGH to liver membranes was three times lower than in normal seawater smolts. The concentration of salmon GH binding sites was decreased in stunt livers by 60%, while their affinity for sGH was unchanged. Down-regulation of hepatic GH receptors by high plasma GH levels may explain in part the low sGH binding in stunts.

Salmon growth hormone is transported into the circulation of rainbow trout, Oncorhynchus mykiss, after intestinal administration

Transport of recombinant salmon growth hormone (rsGH) into the circulation of rainbow trout following intragastric or rectal administration was investigated. Changes in plasma GH levels were analyzed by radioimmunoassay specific to chum salmon GH. Intragastric administration of rsGH by oral intubation resulted in elevation of GH immunoreactivity in plasma after 11h. The plasma GH increased maximally after 15h, and then declined rapidly to reach a normal level after 19h. On the other hand, oral intubation of rsGH to carp, which has no stomach, caused elevation of plasma GH levels after 1 h which lasted for 21 h. In sharp contrast, rectal administration of rsGH to rainbow trout significantly elevated plasma GH levels after 15 min, which reached a maximum after 30 min. The rsGH was labeled with fluorescein isothiocyanate (FITC) to distinguish exogenous from endogenous GH, and administered into rainbow trout rectally. Subsequent analysis of plasma samples on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed two fluorescent bands at the same molecular weights as those of the monomeric and dimeric rsGHs. Intragastric and rectal administration of rsGH into juvenile trout resulted in significant increases in length and body weight compared to the control fish. This study strongly suggests that the rsGH is transported into the circulation of salmonids via the lower part of the intestine and takes part in growth stimulation.

Inhibitory effect of hypothalamic medial preoptic area somatostatin on growth hormone-releasing factor in the rat.

Possible inhibitory effects of somatostatin (SRIF) on GRF were studied by assessing spontaneous GH secretion and GRF content and release in adult male rats depleted of hypothalamic SRIF by anterolateral hypothalamic deafferentation (AHD) or electrolytic lesions in the medial preoptic area (MPO). Plasma GH levels were measured 7 days postoperatively every 20 min in conscious animals with indwelling iv cannulae. Median eminence SRIF was markedly reduced 8 days postoperatively in both AHD and MPO rats, as determined by immunohistochemistry and RIA (P less than 0.01). Although GRF immunoreactivity in the median eminence of AHD and MPO animals appeared well preserved immunocytochemically, hypothalamic GRF content by RIA was significantly decreased at 8 days (P less than 0.01). Spontaneous GH secretion was pulsatile in sham-operated animals. In contrast, basal GH levels in AHD and MPO animals were markedly elevated (P less than 0.01), and secretory pulses were absent. Intravenous injection of specific anti-GRF serum into MPO animals decreased the elevated plasma GH levels (P less than 0.01), indicating increased hypothalamic GRF secretion. GRF release from hypothalamic median eminence-arcuate nucleus complexes in vitro was significantly greater in AHD and MPO animals than in control animals 4 and 8 days postoperatively in response to 30 mM K+ (P less than 0.01), but not under basal conditions. These results suggest that hypothalamic medial preoptic area somatostatinergic neurons play a tonic inhibitory role in the regulation of GRF release and that GH hypersecretion observed after MPO and AHD is attributable to changes in both SRIF and GRF.

Effect of a single administration of somatostatin analogue (SMS 201-995) on GH, TSH and insulin secretion in patients with acromegaly.

The effect of a long-acting somatostatin analogue SMS 201-995 on GH secretion was investigated. Eleven acromegalic patients received a single dose of 50 micrograms SMS 201-995 administered subcutaneously, and plasma GH, IGF-I, GRF, TSH, IRI and blood glucose were determined at regular intervals. Nine of 11 patients had elevated basal plasma GH levels above 5 ng/ml. In all patients, plasma GH levels fell immediately from 39.5 +/- 17.3 ng/ml (mean +/- SEM) to 4.3 +/- 1.6 ng/ml (P less than 0.05) with a maximal inhibition of 82.9 +/- 3.3% of the basal levels and the suppression persisted for about 6 h of the observation period. IGF-I and GRF levels were not apparently altered. TSH and IRI levels also rapidly fell. Blood glucose levels fell slightly by 0.5 h. Ten of 11 patients had pain at injection sites. Except for this, no side effects were observed. Our results show that the new somatostatin analogue SMS 201-995 may inhibit GH hypersecretion in acromegalic patients for significant periods, suggesting that this agent can be a useful clinical tool for the treatment of acromegaly.

Plasma growth hormone responses to microinfusion of noradrenergic agents into or electrical stimulation of the hypothalamus and amygdala in baboons.

In nine baboons (Papio papio) guide cannulae and electrodes were stereotaxically implanted into the medial basal or lateral hypothalamus, the anterior hypothalamus or the dorsal amygdala. Plasma GH responses were measured after microinfusion (1 microliter) of the alpha2 adrenergic agonist, clonidine, or the beta adrenergic antagonist, propranolol, or electrical stimulation, in each of these sites. Clonidine, 100 nmol/microliter, infused into the medial basal or lateral hypothalamus elevated plasma GH levels by 5-30 ng/ml, 30-45 min post-infusion. Plasma GH responses to clonidine infused into the anterior hypothalamus or the dorsal amygdala were all less than 10 ng/ml. The prior, intravenous, administration of piperoxane, 1.0 mg/kg prevented GH responses to clonidine. Propranolol, 50 nmol/microliter, infused into the dorsal amygdala consistently increased plasma GH levels by 5-15 ng/ml. Electrical stimulation of the medial basal or lateral hypothalamus elevated plasma GH levels by 7-35 ng/ml, 15-45 min post stimulation. Electrical stimulation of anterior hypothalamus or dorsal amygdala did not alter plasma GH levels. The stimulation of alpha 2 adrenergic receptors in the medial basal or lateral hypothalamus of the baboons appears to facilitate GH release.

Responses to epinephrine in patients with anorexia nervosa.

To examine the sensitivity to epinephrine in patients with anorexia nervosa, 20-60 micrograms/kg body weight/min of epinephrine was infused for 30 min each in 5 patients and 5 controls. The increase in pulse rate and the decrease in diastolic blood pressure were significantly smaller in the patient group. Elevated plasma GH levels in the patients were markedly suppressed by epinephrine infusion. These results indicate the beta-adrenergic function is decreased at least in the cardiovascular system in patients with anorexia nervosa.

Acromegaly Associated with a Bronchial Carcinoid Tumor: Evidence for Ectopic Production of Growth Hormone-Releasing Activity*

A patient with acromegaly, pituitary enlargement, and elevated plasma GH levels also had a bronchial carcinoid tumor. Signs and symptoms of active acromegaly along with elevated GH levels persisted for 11 yr after hypophysectomy and pituitary stalk section. Resection of the bronchial carcinoid reduced plasma GH to barely detectable levels. Extracts of the frozen carcinoid tumor were devoid of significant GH, but when added to isolated pituitary cells of estrogen-primed male rats in 4-day primary culture exhibited specific GH-releasing activity in vitro. These findings strongly suggest that the patient's acromegaly resulted from continual stimulation of pituitary somatotrophs by a GH-releasing factor secreted by the bronchial carcinoid.

Somatostatin content of the median eminence in female rats with lesion-induced disruption of the inhibitory control of growth hormone secretion.

These experiments were designed to determine whether brain lesions which elevate nonstress plasma levels of GH and disrupt stress-induced suppression of GH secretion in female rats affect the median eminence content of somatostatin. Some rats received lesions in the medial or lateral preoptic-anterior hypothalamic area (PO-AHA), while others received anterior hypothalamic cuts. Sham-operated and intact rats served as controls. GH and somatostatin were measured by RIA. Medial but not lateral PO-AHA lesions caused elevated nonstress plasma GH levels at 2, 14, 17, and 23 weeks after surgery, but normal levels were obtained at autopsy at 27 weeks. These lesions compromised GH responses to stress at 14 and 23 weeks. Rats with anterior hypothalamic cuts showed elevated nonstress GH levels at 17, 23, and 27 weeks after surgery and loss of the GH response to stress at 14 and 23 weeks. Median eminence content of somatostatin was reduced approximately 80% in rats with medial PO-AHA lesions or anterior cuts. Whereas medial PO-AHA lesions were associated with normal body length and weight and evidence of estrogen secretion, anterior hypothalamic cuts produced increased linear growth and body weight and signs of functional castration. These results suggest that the effects of lesions which cause prolonged elevation of nonstress GH levels and disruption of the GH stress response are due to interference with somatostatin neurons located in the medial PO-AHA. Somatostatin content of the median eminence seems to depend largely on connections originating in or traversing the medial PO-AHA.