Biomedical subjects

C Dieguez

Publications and source records attributed to C Dieguez.

At least 145 records · Page 8Linked to original sources

PubMed1993

Influence of hyperthyroidism on growth hormone secretion.

OBJECTIVE: Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue. DESIGN: Study 1: GHRH (1 microgram/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of the patients the GHRH test was repeated following methimazole-induced remission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were administered 3 hours prior to GHRH; six hyperthyroid patients and six normal subjects were studied. Study 3: ten normal subjects and ten hyperthyroid patients were given 75 g oral glucose or water 30 minutes before GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients were studied. TRH or vehicle were dissolved in 250 ml of saline solution and infused at a rate of 400 micrograms/h for 150 minutes. Thirty minutes after the beginning of the infusions, L-arginine (30 g infused over 45 min i.v.) was administered. PATIENTS: Hyperthyroid patients were compared to normal subjects. MEASUREMENTS: Growth hormone was measured by RIA at 15-minute intervals. RESULTS: GH responses to GHRH were subnormal in hyperthyroid patients. Following antithyroid drug treatment with methimazole, GH responses to GHRH increased in these patients in comparison to pretreatment values. Serum IGF-I levels, which were elevated before treatment, decreased after methimazole administration. Exogenous GH administration induced a clear decrease of GH responses to GHRH in both control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthyroid subjects. TRH administration did not modify the GH responses to arginine in either normal subjects or hyperthyroid patients. CONCLUSIONS: Hyperthyroidism is associated with increased serum IGF-I levels and marked alterations in the neuroregulation of GH secretion. These changes involve decreased GH responsiveness to GHRH at the pituitary level and, at the hypothalamic level, a lack of suppressive effect of an oral glucose load. The normal inhibitory effect of exogenous GH administration but not of an oral glucose load in hyperthyroid patients suggests that these two feedback signals act through different mechanisms. The lack of effect of a TRH infusion on GH responses to L-arginine in normal and hyperthyroid patients makes an inhibitory role for TRH in GH secretion unlikely, at least in Caucasian subjects.

Adult↗

PubMed1993

Growth hormone releasing hormone priming increases growth hormone secretion in patients with Cushing's syndrome.

OBJECTIVE: In patients with Cushing's syndrome, decreased growth hormone (GH) secretion is observed though the basic mechanism is unknown. In states of chronic deficiency of hypothalamic growth hormone releasing hormone (GHRH) release, a blunted GH response to exogenous GHRH has been reported; such impairment can be partially normalized by repetitive GHRH administration (priming). In order to clarify whether a deficit in hypothalamic release of GHRH is the basis of the decreased GH secretion in patients with Cushing's syndrome, GHRH plus pyridostigmine tests were undertaken, both before and after GHRH priming. DESIGN: GHRH (200 micrograms/day as a single s.c. injection) was given daily over 7 days. Two pyridostigmine (120 mg p.o.) plus GHRH (100 micrograms i.v.) tests were performed before and after priming to assess GH response. PATIENTS: Eight patients (seven women, one man), with untreated Cushing's syndrome (six Cushing's disease, one autonomous bilateral adrenal hyperplasia, one adrenal adenoma), were studied. MEASUREMENTS: Plasma GH levels were measured by immunoradiometric assay. RESULTS: GHRH plus pyridostigmine-induced GH release was impaired in patients with untreated Cushing's syndrome (mean peak 5.2 +/- 1.4 mU/l, area under the curve (AUC) 472 +/- 96). Repetitive administration of GHRH over 7 days partially restored the GH response to the second pyridostigmine-GHRH test (mean peak 15.0 +/- 2.1 mU/l. AUC 1016 +/- 104), both P < 0.05. All of the eight Cushing's syndrome patients studied presented a higher GHRH plus pyridostigmine-induced GH secretion after priming. CONCLUSIONS: Repetitive administration of GHRH increases the pyridostigmine-GHRH-induced GH secretion in patients with Cushing's syndrome. This suggests that impaired hypothalamic release of GHRH is a contributing factor to the decreased GH secretion observed in chronic hypercortisolism.

Adult↗

PubMed1993

Influence of sex, age and adrenergic pathways on the growth hormone response to GHRP-6.

OBJECTIVE: His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species including man. To further characterize the effects of GHRP-6 on GH secretion in normal human subjects, we assessed plasma GH levels following GHRP-6 administration in normal male adult subjects, normal female adult subjects at different stages of their menstrual cycle and in normal prepubertal male and female children. We also studied the influence of adrenergic pathways on GHRP-6 induced GH secretion in normal adult male subjects. DESIGN: In a group of eight volunteers the following tests were carried out: GHRP-6 alone (1 microgram/kg i.v. at 0 minutes); propranolol (40 mg p.o. at -30 minutes) plus GHRP-6; and prazosin (3 mg p.o. at -120 minutes) plus GHRP-6. Another group of eight volunteers were studied with GHRP-6 as above; clonidine alone (300 mg p.o. at -60 minutes); and clonidine plus GHRP-6. A group of nine women were studied with 1 microgram/kg i.v. of GHRP-6 at 0 minutes, at different stages of their menstrual cycle. Finally, 12 children were studied with GHRP-6 using the same dose and methods as above. PATIENTS: Twenty-five normal adult subjects (16 male and nine female) and 12 normal prepubertal children (six male and six female) wer studied after giving informed consent. MEASUREMENTS: Plasma GH levels were measured by radioimmunoassay. RESULTS: No differences in GH responses to GHRP-6 were found between children and normal adult male or female subjects at different stages of their menstrual cycle. Administration of propranolol and clonidine did not modify the GH responses to GHRP-6 in male adults. In contrast, prazosin administration induced an increase in plasma GH levels that was statistically different from that of GHRP-6 alone (. < 0.05 between area under curve). CONCLUSIONS: GHRP-6 exerts a potent stimulatory effect on GH secretion in adults and children. Its effects, at least at the dose studied, are independent of sex and age. Noradrenergic pathways through alpha 2 adrenergic receptors are unlikely to influence this response.

Adult↗

PubMed1993

Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-induced GH secretion in the rat.

His-dTrp-Ala-Trp-dPhe,Lys-NH2(GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 micrograms/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 micrograms/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexamethasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while dexamethasone did not affect the GH responses to GHRH, highlighting a differential regulation of these hormones on somatotroph responsiveness to these peptides.

Amino Acid Sequence↗

PubMed1993

Regulation of prothymosin alpha mRNA levels in rat pituitary tumor cells.

Prothymosin alpha (PTA) mRNA and histone H4 (H4) mRNA levels were studied in various experimental conditions that affected GH1 pituitary tumor cell proliferation. Cell proliferation and progression through the cell cycle was assessed by counting cells, 3H-thymidine incorporation and flow cytometry. PTA mRNA levels were decreased in a time-dependent fashion following serum deprivation; when the cells were induced to grow by serum refeeding, PTA mRNA expression was greatly stimulated. Interestingly, after caprylic acid treatment (2.5 mM for 24 h) that arrested cells in the G0/G1 phase of the cell cycle, PTA mRNA and H4 mRNA levels were almost undetectable; conversely, following caprylic acid withdrawal, PTA mRNA and H4 mRNA expression were greatly stimulated. Furthermore, cells cultured in T3-deprived serum, which was found to decrease GH1 cell proliferation, had low levels of PTA and H4 mRNAs. This effect was reversed by the addition of nanomolar concentrations of T3 to the culture. On the other hand, IGF-1 addition to the culture did not substantially modify PTA mRNA levels. The present data clearly indicate that PTA mRNA expression is tied to the proliferating activity of GH1 cells and, thus, could be used as a marker of the action that various agents have on GH1 cell proliferation.

Actins↗

PubMed1993

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man.

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.

Adult↗

PubMed1993

Pyridostigmine potentiates growth hormone (GH)-releasing hormone-induced GH release in both men and women.

It has been recently reported that pyridostigmine (PD), an indirect cholinergic agonist, probably acting via inhibition of hypothalamic somatostatin, potentiates the GH-releasing hormone (GHRH)-induced GH rise in men, but not in women. The aim of this study was to verify the sex-related, if any, GH response to GHRH (1 microgram/kg, i.v., as a bolus) both alone and preceded by two different doses of PD (120 mg, group A, and 60 mg, group B, given orally 60 min before GHRH) in a large group of volunteers (36 women, aged 18-35 yr, and 48 men, aged 18-35 yrs). In group A, 120 mg oral PD potentiated the GH response to GHRH in both men [area under the curve (AUC), 2579.3 +/- 264.5 vs. 806.2 +/- 99.7 micrograms/L.h; P < 0.00001] and women (AUC, 2273.2 +/- 248.7 vs. 792.6 +/- 72.7 micrograms/L.h; P < 0.00001). Similarly, in the group B, 60 mg oral PD potentiated the GH response to GHRH in both men (AUC, 1929.6 +/- 157.2 vs. 568.2 +/- 81.3 micrograms/L.h; P < 0.01) and in women (AUC, 1655.9 +/- 146.9 vs. 738.2 +/- 105.7 micrograms/L.h; P < 0.01). The GH responses to GHRH, both alone and after 120 and 60 mg oral PD, did not significantly differ in men and women. No sex-related difference was observed in the cholinergic side-effects (mild abdominal pain and muscle fasciculations) that occurred in nearly 30% of the subjects. In conclusion, our results clearly show that there is no sex-related difference in the potentiating effect of PD on GHRH-induced GH release, ruling out the suggestion that women have increased cholinergic activity, leading to reduced somatostatinergic tone.

Adolescent↗

PubMed1993

Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity.

GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.

Adolescent↗

PubMed1993

Evidence against depletion of the growth hormone (GH)-releasable pool in human primary hypothyroidism: studies with GH-releasing hormone, pyridostigmine, and arginine.

We investigated whether the impaired GH secretion of hypothyroid patients could be due to an increase in hypothalamic somatostatinergic tone. Twenty-four patients with primary hypothyroidism [20 females and 4 males; mean age (+/- SE), 47.5 +/- 2.7 yr] and 20 normal subjects (17 females and 3 males; age, 47.6 +/- 3.0 yr) were studied. In the first group of 12 hypothyroid patients, administration of pyridostigmine, a cholinergic agonist drug (120 mg, orally, at -60 min), notably increased GH responses to GH-releasing hormone (GHRH; 1 microgram/kg, iv, at 0 min; peak GH levels for pyridostigmine plus GHRH vs. placebo plus GHRH, 16.6 +/- 4.9 vs. 6.0 +/- 1.8 micrograms/L; P < 0.01). The GH responses to pyridostigmine plus GHRH, however, were considerably lower than those in 10 normal subjects (peak GH levels, 53.0 +/- 3.5 micrograms/L; P < 0.001). In the second group of 12 hypothyroid patients, arginine infusion (30 g, iv, from 0-30 min) markedly increased the GH responses induced by GHRH administration (1 microgram/kg, iv, at 0 min; peak GH levels for arginine plus GHRH vs. placebo plus GHRH, 30.6 +/- 4.7 vs. 5.3 +/- 1.0 micrograms/L; P < 0.001). However, GH release after GHRH plus arginine was greater in 10 normal subjects than in the hypothyroid patients (peak GH levels, 50.9 +/- 5.3 micrograms/L; P < 0.001). Pyridostigmine and arginine inhibit hypothalamic somatostatin tone. The stimulatory effect of both agents on GHRH-induced GH release indicates that reduced GH secretion in hypothyroidism can be reversed to a considerable extent by inhibiting hypothalamic somatostatinergic tone. The relatively greater potency of arginine compared to pyridostigmine suggests that hypothyroid patients may have an impairment of the cholinergic pathways. Furthermore, these data show that hypothyroid patients have a somatotrope secretory capacity much greater than previously thought.

Adult↗

PubMed1993

Prothymosin alpha mRNA is expressed in competent and proliferating rat thyroid cells (FRTL-5) but is not sufficient to elicit cell progression through the cell cycle.

Using flow cytometry we observed the effects that different hormonal treatments had on the progression of rat thyroid (FRTL-5) cells through the cell cycle. The absence of hormones or the addition of TSH (6 mU/ml) did not induce DNA synthesis; however, the addition of IGF-I (30 ng/ml) promoted cell proliferation. The number of cells recruited by IGF-I was lower than when IGF-I and TSH were used. We therefore concluded that we had a model with three different types of cells: (1) quiescent cells, cells cultured in the absence of hormones, considered to be G0-arrested cells, (2) competent cells, TSH-treated cells that did not proliferate (being arrested in a cycle phase different from G0) and (3) actively proliferating cells, cells treated with TSH plus IGF-I. Prothymosin alpha (PTA) mRNA levels were almost undetectable in cells cultured without hormones at all times studied, i.e. 8, 14 and 24 h. On the contrary, TSH and/or IGF-I greatly increased PTA mRNA. These data indicate that G0-arrested quiescent cells do not express PTA mRNA and that PTA mRNA is induced when FRTL-5 cells are committed to proliferate by the addition of TSH, in spite of being arrested by the lack of IGF-I. We therefore conclude that PTA mRNA expression may be an event that is necessary for cells to proliferate, but that it is not sufficient for the promotion of cell progression through the cell cycle.

Animals↗

PubMed1993

Influence of endogenous cholinergic tone and alpha-adrenergic pathways on growth hormone responses to His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in the dog.

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and alpha-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed. In adult Beagle dogs (n = 10), GHRP-6 (90 micrograms i.v.) increased basal GH levels from 2.6 +/- 1.5 to 14.4 +/- 3.1 micrograms/l (mean +/- S.E.M.) after 15 min. GHRH (50 micrograms i.v.) induced a GH peak of 9.7 +/- 2.2 micrograms/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 +/- 9.0 micrograms/l (P < 0.01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37.9 +/- 10.1 micrograms/l P < 0.05), while the muscarinic blocker atropine (100 micrograms i.v.) completely abolished (GH peak lower than 2 micrograms/l) the stimulatory action of GHRP-6. On the other hand, administration of the alpha-2 adrenergic agonist clonidine (4 micrograms/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Differential effects of in vivo estrogen administration on hypothalamic growth hormone releasing hormone and somatostatin gene expression.

The aim of this study was to investigate the effect of in vivo estrogen administration on hypothalamic growth hormone releasing hormone (GHRH) and somatostatin (SS) gene expression. We found that estrogen administration (estradiol valerate 250 micrograms/every 3 days, subcutaneously) to male rats induced a decrease in both hypothalamic GHRH mRNA levels and GHRH content, that was significant after 3 and 8 days of treatment. In contrast SS mRNA levels were transiently elevated after 1 and 3 days of estrogen administration, returning to normal values after 8 days of treatment. These data suggest that the existence of sexual dimorphism in GH secretion in the rat could be mediated to some extent by gonadal hormones regulating somatostatin and GHRH gene expression in the hypothalamus.

Animals↗

PubMed1992

Stimulatory effect of free fatty acids on growth hormone releasing hormone secretion by fetal rat neurons in monolayer culture.

The effects of free fatty acids (FFAs) on growth hormone releasing hormone (GHRH) secretion by fetal rat cortical and hypothalamic neurons in monolayer culture have been investigated. Treatment with caprylic or oleic acids for 90 min, induced a dose-dependent increase in GHRH secretion. The stimulatory effect of caprylic acid was time-dependent, being present after 90 min and 5 h but not after 24 h. Finally, GHRH release induced by 56 mM KCl or by the calcium ionophore A23187 was not modified by 5 x 10(-3) M caprylic acid. These data support a role for FFAs on GHRH secretion.

Animals↗

PubMed1992

Differential effects of arginine on growth hormone releasing hormone and insulin induced growth hormone secretion.

OBJECTIVE: We wished to investigate the interaction of arginine, GHRH and insulin stress on GH secretion. DESIGN: Six healthy, non-obese volunteers underwent seven separate studes in random order. They received (1) insulin alone at 0 minutes; (2) GHRH alone at 15 minutes; (3) arginine alone at 0-30 minutes; (4) arginine at 0-30 minutes and GHRH at 15 minutes; (5) insulin at 0 minutes and arginine at 0-30 minutes; (6) insulin at 0 minutes, GHRH at 15 minutes and arginine at 0-30 minutes; (7) insulin at 0 minutes and GHRH at 15 minutes. MEASUREMENTS: GH and PRL were measured from -30 to 150 minutes at intervals of 15 minutes. RESULTS: Arginine increased GH responses to GHRH and decreased GH responses to hypoglycaemia, but this inhibitory effect of arginine was reversed by GHRH. CONCLUSIONS: The findings suggest that arginine-induced GH release is mainly mediated by a decrease in somatostatinergic tone, while GH responses to insulin stress are probably mediated by both an increase in hypothalamic GHRH release and inhibition of somatostatin.

Adult↗

PubMed1992

Effect of retinoic acid deficiency on in vivo and in vitro GH responses to GHRH in male rats.

Retinoic acid has recently been shown to increase growth hormone (GH)-gene transcription rate and GH synthesis in vitro. To investigate the role retinoic acid plays in the neuroregulation of GH secretion we have studied GH responses to growth hormone-releasing hormone (GHRH) in retinoic acid-deficient rats. Compared to normally fed male rats, retinoic acid-deficient rats showed a marked impairment in body weight, which was statistically significant after 3 weeks and maximal after 5-6 weeks (p less than 0.001). Yet, in vivo GH responses to different doses of GHRH (1, 5 and 25 micrograms/kg) in pentobarbital-anesthesized rats were similar in both groups. Also, in vitro GH responses to GHRH, forskolin, and KCl were similar in perfused pituitary cells taken from control and retinoic acid-deficient rats. However, further studies carried out in freely-moving rats showed the typical GH secretory pattern usually found in male rats of the control group, while retinoic acid-deficient rats displayed a highly variable GH secretory pattern with GH peaks of much lower amplitude. Finally, after gel electrophoresis of in vitro 35S-labelled proteins, no differences were observed in the molecular forms of GH. Considering these findings on normal pituitary responsiveness and alterations in GH pulsatility, our data suggest that retinoic acid deficiency leads to an alteration in the neuroregulation of GH secretion at the central level.

Animals↗

PubMed1992

Corticoid-induced growth hormone (GH) secretion in GH-deficient and normal children.

Acute administration of corticoids is a potent stimulus of GH secretion in man. To ascertain their mechanism and point of action as well as the suitability of this novel test in the diagnosis of GH-deficient states, normal controls and GH-deficient children were studied. They were selected based on auxological criteria and the GH response to provocative stimuli. The GH-deficient children presented a blunted GH (mean +/- SEM; microgram/L) discharge after insulin-induced hypoglycemia (2.9 +/- 0.4), propranolol-exercise (7.4 +/- 1.5), and clonidine (6.5 +/- 0.8) compared with values in the normal children (7.2 +/- 2.2, 15.8 +/- 2.4, and 15.6 +/- 1.8, respectively). As expected, GH-releasing hormone (GHRH)-induced GH discharge in GH-deficient children (33.2 +/- 4.9) was similar to that in the control children (35.1 +/- 6.0). Administration of 2 mg/m2 body surface dexamethasone, iv, to normal children induced, 3 h later, a mean GH peak of 14.1 +/- 1.2 micrograms/L. This was significantly higher that the corticoid-induced GH peak in GH-deficient children (6.7 +/- 1.1 micrograms/L). The corticoid-induced areas under the secretory curve were 1130 +/- 55 and 616 +/- 54 for the control and GH-deficient children, respectively. GH release in children after dexamethasone administration followed the pattern previously described for adults, i.e. there were no modifications of basal GH levels in the first 2 h, the GH peak appeared around the third hour, and the GH levels remained increased until the fourth hour after dexamethasone administration. Individually considered, practically all control children, but only 2 of 12 GH-deficient children, presented a dexamethasone-induced GH peak over the 10 micrograms/L level. In both normal and GH-deficient patients, corticoids appeared just as potent a stimulus as propranolol-exercise and clonidine, and more potent than hypoglycemia. This new stimulus showed a pattern similar to that of the hypothalamic stimuli, but clearly different with respect to the pituitary one (GHRH), suggesting that corticoids activate GH secretion by acting at hypothalamic level. In conclusion, acute administration of corticoids could be a suitable test in the diagnostic armamentaria of GH-deficient states.

Adolescent↗

PubMed1991

Role of growth hormone-releasing hormone on pentagastrin-induced growth hormone release in normal subjects.

In order to investigate the mechanisms by which gastrin cause GH release in humans we measured the GH response to pentagastrin alone (1.5 micrograms/kg/hour from 120 to 210 min) and following pretreatment with GHRH (GHRH 1-29,250 micrograms, iv at 0 min) in normal male subjects. Prior GHRH administration abolished the GH response to the second bolus of GHRH (1 micrograms/kg) administered two hours later. Pentagastrin infusion induced a rise in GH levels maximal at 60 min (9.1 + 0.6 ng/ml, mean + SE), but this rise was abolished by pretreatment with GHRH. Finally, we found that gastrin did not modify basal GH release or GH responses to GHRH by rat anterior pituitary cells in monolayer culture. Taken together, these data suggest that gastrin regulates GH secretion by acting at hypothalamic level.

Adult↗

PubMed1991

Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients.

OBJECTIVE: We wished to investigate whether thyrotoxicosis can influence the cholinergic modulation of GH secretion. DESIGN: Pyridostigmine was given orally, then GHRH injected i.v., and levels were measured. In a separate study, pirenzepine was injected i.v., then GHRH, and growth hormone levels were measured. PATIENTS: Thyrotoxic patients were compared with normal subjects. MEASUREMENTS: GH was measured from -30 to +120 minutes at intervals of 15 minutes. RESULTS: Pyridostigmine markedly increased GH responses to GHRH in normal subjects, but not in thyrotoxic patients. Pirenzepine abolished the GH response to GHRH in thyrotoxic patients. CONCLUSIONS: GH responses to GHRH in hyperthyroid patients were suppressed by cholinergic muscarinic receptor blockade with pirenzepine. Activation of cholinergic pathways with pyridostigmine did not increase GH responses to GHRH in these patients. This may be a consequence of increased hypothalamic cholinergic function or reduced hypothalamic GHRH activity in hyperthyroidism. Our findings demonstrate a further mechanism by means of which thyroid status may affect the secretory activity of the somatotroph.

Adolescent↗