Biomedical subjects

C Dieguez

Publications and source records attributed to C Dieguez.

At least 109 records · Page 6Linked to original sources

PubMed1997

Influence of endogenous leptin tone on the estrous cycle and luteinizing hormone pulsatility in female rats.

Recent data indicate that leptin may well play an important regulatory role in the hypothalamo-pituitary-gonadal axis. In order to further unravel the mechanisms by which leptin acts, we have studied the effect of treatment (8 days) of leptin antiserum (5 microl daily; i.c.v.) on LH pulsatility and estrous cycle in adult female rats. The administration of leptin antiserum led to a marked decrease in LH pulsatility as assessed by the area under the curve (13.5 +/- 4.7 ng/ml) in comparison to rats treated with normal rabbit serum (114 f 53 ng/ml; p < 0.01). Furthermore, rats treated with leptin antiserum showed an impairment of reproductive function as shown by the fact that all rats remained in anestrus. In conclusion, these data show that leptin markedly influences LH secretion and the estrous cycle in the female rat.

Animals↗

PubMed1997

Synthesis of leptin in human placenta.

UNLABELLED: Gender-based differences in serum leptin levels have been reported in umbilical cord blood, and leptin has been detectedin human amniotic fluid. In order to understand if leptin may be directly synthesized by human placentae an analysis made up of several steps was performed. First at all RT-PCR analysis from placenta-derived RNA was used to detect human leptin mRNA. The leptin-like immunoradioactivity detected in placentae extracts was identical to human leptin according to the criteria of charge, immunorecognition, SDS-PAGE analysis and blotting, indicating that intact leptin was found and no variants in size, charge or immunoactivity were present in the placentae. Finally an immunohistochemical analysis showed the presence of leptin in the cytoplasm of syncytiotrophoblast cells but not in the core of villi. IN CONCLUSION: leptin is synthesized as a single molecular variant identical to human recombinant leptin in human placentae at delivery.

Base Sequence↗

PubMed1997

Leptin inhibits in vitro hypothalamic somatostatin secretion and somatostatin mRNA levels.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. The site of action of leptin is likely to be the hypothalamus, since this area is important in the control of food intake and leptin receptor mRNA is particularly abundant in this area. In order to further unravel the mechanisms by which leptin acts, we have studied the effect of leptin on in vitro somatostatin synthesis and secretion. Leptin administration to fetal rat neurones in monolayer culture led to a time dependent decrease in basal somatostatin secretion and somatostatin mRNA levels, the maximal effect being observed with 6x10(-8) M leptin after 24 h incubation. Furthermore, leptin completely blunted 10(-7) M Neuropeptide Y-induced increase in somatostatin secretion and somatostatin mRNA levels as well as 10(-3) M (Bu)2-cAMP and 10(-6) M A23187-induced somatostatin secretion. Finally, leptin (3x10(-8) M M) also inhibited low glucose (1.1 mM) induced-somatostatin secretion in perifused adult hypothalami. This data indicates that leptin can influence the neuroendocrine system by regulating hypothalamic somatostatin gene expression.

Aging↗

PubMed1997

Regulation of in vivo growth hormone secretion by leptin.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Growth hormone (GH) secretion is markedly influence by body weight being markedly suppressed in obesity and underweight. The aim of the present study was to study whether leptin can act as a metabolic signal connecting the adipose tissue with the growth hormone axis. We administered leptin antiserum (10 ul, i.c.v.) or normal rabitt serum (NRS; 10 ul, i.c.v.) to freely moving fed rats. Furthermore we assessed the effect of leptin administration (10 ug, i.c.v.) on fed and fasted rats. Spontaneous GH secretion was assessed over 6 hours with blood samples taken every 15 min. Administration of leptin antiserum led to a decrease in spontaneous GH secretion as assessed by the area under the curve (AUC) (168+/-72 ng/ml/6h) in comparison to NRS-treated rats (813+/-179 ng/ml/6h, p<0.01). While leptin administration (10 ug/rat; i.c.v.) to normal fed rats did not modify spontaneous GH secretion, leptin administration to fasted rats led to a reversal of the inhibitory effect exerted by fasting on GH secretion (AUC, 1650+/-351 ng/ml/6h vs 77+/-32 ng/ml/6h, p<0.01). This data suggests that leptin is a metabolic signal that regulates GH secretion.

Activity Cycles↗

PubMed1997

Influence of thyroid status on serum immunoreactive leptin levels.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that, little is known about the physiological actions of leptin in humans. The aim of this study was to assess the influence of hypo- and hyperthyroidism on serum leptin levels. Thirty-two patients (16 with hypothyroidism and 16 with hyperthyroidism) were studied before and after treatment with replacement doses of T4 (hypothyroid patients) or methimazole (hyperthyroid), when thyroid function was normal. Control serum for each group was obtained from healthy age-, sex-, and body mass index-matched subjects. Plasma leptin levels were measured by specific RIA. The mean leptin level in the hypothyroid patients was lower before treatment (4.7 +/- 0.7 microg/L) than that in the controls (8.6 +/- 1.4 microg/L; P < 0.02) and was lower than that during treatment with T4 and normalization of thyroid function in the same group of patients (6.3 +/- 0.8 microg/L; P < 0.05). Leptin levels in the hyperthyroid patients were similar before (7.2 +.0 1.1 microg/L) and after normalization of thyroid function following treatment with methimazole (6.2 +/- 1.1 microg/L) and were similar to the control value (8.8 +/- 1.4 microg/L). In conclusion, leptin levels are decreased in the hypothyroid patients and unchanged in hyperthyroidism. Whether decreased leptin levels may contribute to the decreased energy expenditure in patients with hypothyroidism merits further investigation.

Female↗

PubMed1997

Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome.

We studied 24-h profiles of circulating leptin levels using a sensitive and specific radioimmunoassay in healthy pre- (Tanner 1) and pubertal boys and girls (Tanner 3-4) as well as in a group of patients with perinatal stalk-transection syndrome. Similar nyctohemeral rhythm in serum leptin levels were found in prepubertal (MESOR: 2.34 +/- 0.2 ng/ml; amplitude 0.32 +/- 0.1 ng/ml) and pubertal boys (MESOR 2.2 +/- 0.2 ng/ml; amplitude 0.38 +/- 0.07 ng/ml). Likewise, no differences were found between prepubertal (MESOR 6.6 +/- 1.07 ng/ml; amplitude 1.67 +/- 0.4 ng/ml) and pubertal girls (MESOR 4.05 +/- 0.5 ng/ml; amplitude 0.95 +/- 0.2 ng/ml). In contrast, higher MESOR (p < 0.002) and amplitude values (p < 0.005) were found in prepubertal and pubertal girls than in prepubertal and pubertal boys. Finally a significant nyctohemeral rhythm in serum leptin levels was found in patients with perinatal stalk-transection syndrome (MESOR: 9.3 +/- 2.3 ng/ml; amplitude 1.46 +/- 0.4 ng/ml). This data shows the existence of sexual dimorphism in the nyctohemeral rhythm in serum leptin levels that are not influenced by the pubertal stage or by pulsatile anterior pituitary hormone secretion.

Adolescent↗

PubMed1997

Acute pharmacological reduction of plasma free fatty acids enhances the growth hormone (GH)-releasing hormone-mediated GH secretion in patients with Cushing's syndrome.

In Cushing's syndrome, GH secretion is blocked with all the stimuli tested. It has been reported that the acute pharmacological reduction of free fatty acids (FFA) leads to an enhancement of GH secretion in normal subjects and in pathological conditions associated with reduced GH secretion. To understand if the elevated FFA levels of hypercortisolism may be responsible for the altered GH secretion, 14 patients with active Cushing's syndrome underwent 2 paired tests with 100 micrograms i.v. of GHRH on 2 different occasions. In one test, they were pretreated with placebo and in the other one, with acipimox 250 mg p.o. 4 h before, and 250 mg p.o. 1 h before GHRH. The basal FFA levels (799 +/- 57 mmol/L) were reduced by acipimox throughout the whole test (values under 240 +/- 28 mmol/L). In the placebo pretreated group, GHRH-induced GH secretion was severely impeded, with a mean GH peak of 1.8 +/- 0.3 micrograms/L and area under the curve of 121.3 +/- 21.6 micrograms/L-120 min. All the patients showed a GHRH-mediated GH peak under 4 micrograms/L. Acute reduction of FFA by acipimox enhanced the GHRH action, with a mean GH peak of 11.1 +/- 1.8 micrograms/L and area under the curve of 652.9 +/- 110.3 micrograms/L-120 min (both P < 0.005). Individually analyzed after acipimox, all 14 subjects presented an enhancement in the GHRH-mediated GH peak, and 8 patients showed a response over 10 micrograms/L. In conclusion, acute FFA reduction by acipimox increased the GH secretion elicited by GHRH in chronic hypercortisolism. Elevated FFA may be a contributing factor to the deranged GH secretion observed in Cushing's syndrome.

Adult↗

PubMed1997

Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage.

UNLABELLED: It is commonly accepted that at least in girls puberty starts when a minimum level of body mass or a certain amount of body fat are present. However the precise signal by which adipose stores inform the hypothalamus of the degree of energetic reserves is unknown. Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. To understand whether leptin is the adipose tissue signal that allows puberty, 789 normal children of both sexes, age 5-15 yr, were transversally studied. Leptin levels, as well as gonadal and gonadotropins, levels, were analyzed in addition to the determination of auxological parameters. In an age-related analysis, leptin levels in girls rose from 5-15 yr (from 4.3 +/- 0.4 to 8.5 +/- 0.9 micrograms/L) in parallel with body weight. Boys always had lower leptin levels than girls (3.3 +/- 0.3 micrograms/L at 5 yr), but they rose in parallel with weight until 10 yr (5.3 +/- 0.7 micrograms/L), when a striking decrease was observed until 15 yr (3.0 +/- 0.3 micrograms/L). In girls, leptin was the first hormone to rise followed by FSH and later by LH and estradiol. A similar pattern occurred in boys, despite the fact that leptin dropped after 10 yr when testosterone rises. Divided into three pubertal stages, i.e. P1 = prepuberty, P2 = early puberty, and P3 = overt puberty, in girls the four hormones rose progressively from P1 to P3, but from P2 to P3 the present increment was greater for LH and estradiol. In boys, leptin decreased from P1 to P3, whereas FSH, LH, and testosterone rose. The age-related changes were not caused by adiposity variations, because data did not change when subtracting values of children over 97% of standard deviation score of body mass index. IN CONCLUSION: 1) leptin appears to increase in both boys and girls before the appearance of other reproductive hormones related to puberty; 2) leptin levels in boys are always lower than in girls, although they increase with age until the age 10 yr; 3) leptin in boys declines about the time testosterone increases. Leptin may well be a permissive factor for the initiation of pubertal events.

Adolescent↗

PubMed1997

Sex-based differences in serum leptin concentrations from umbilical cord blood at delivery.

Sex-based differences in serum leptin concentrations have been reported in adolescence and adulthood. To discover when such differences were generated, serum leptin concentrations were measured in umbilical cord blood from 46 healthy infants and in the mother's blood at delivery. Considering the respective body weights of the mothers and infants (68.5 +/- 1.3 kg and 3.3 +/- 0.0 kg), umbilical cord concentrations of leptin were disproportionately high in the infants (9.4 +/- 1.2 micrograms/l) compared with those in the mothers (18.7 +/- 1.3 micrograms/l). There was a wide variation in the infants leptin values (1.2 +/- 56.8 micrograms/l) that did not correlate with height, weight, cephalic circumference, or any other growth-related parameter. The most striking differences emerged when results were analysed by sex: umbilical cord concentrations of leptin in the girls (12.9 +/- 2.2 micrograms/l) were significantly (P < 0.01) greater than those in the boys (6.8 +/- 0.9 micrograms/l), although no differences in leptin concentrations were observed between the mothers who gave birth to a girl (19.5 +/- 2.2 micrograms/l) and those who gave birth to a boy (18.1 +/- 1.7 micrograms/l). The sex-based differences were not attributable to any growth-related differences between the sexes, except heavier placental weights in the girls (P < 0.007) than in the boys. These differences in leptin concentrations may reflect a sex-based difference in the regulation of leptin production by the fetal adipose tissue.

Adult↗

PubMed1997

Leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome.

The study was conducted to assess leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome (PCOS). Twenty-two women with PCOS and 19 control healthy women were included in the study, divided into obese and non-obese groups. Leptin was determined using Linco Research radio-immunoassay while insulin sensitivity was calculated from intravenous glucose tolerance tests with frequent blood sampling using MINMOD analysis. Significantly higher basal leptin levels were found in obese compared to non-obese PCOS (31.76 +/- 3.06 vs. 10.42 +/- 2.31 ng/ml; p < 0.05) as well as in obese in comparison to non-obese controls (29.16 +/- 5.06 vs 8.51 +/- 0.88 ng/ml; p < 0.05). A negative correlation was found between insulin sensitivity and leptin levels in both obese (r = -0.2480; p > 0.05) and non-obese PCOS groups (r = -0.4620; p > 0.05). In conclusion, high serum leptin, insulin and testosterone levels together with reduced insulin sensitivity were found in obese PCOS women, suggesting that high leptin levels could be a characteristic of the obese PCOS phenotype.

Adult↗

PubMed1996

Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

Adult↗

PubMed1996

The sequential administration of growth hormone-releasing hormone followed 120 minutes later by hexarelin, as an effective test to assess the pituitary GH reserve in man.

OBJECTIVE: GH deficiency, either in children or in adults, is a clinically relevant problem. The diagnosis is based on dynamic tests of GH secretion, which are clear cut on a group basis but highly problematic for individual diagnosis. The controversy surrounding the diagnosis of GH deficiency reflects the absence of a gold standard dynamic test. The synthetic hexapeptide hexarelin and GHRH stimulate GH secretion using different mechanisms. A sequential test has been devised using the administration of GHRH as first stimulus followed 120 minutes later by hexarelin. The two aims of the study were (a) to evaluate the interaction of GHRH and hexarelin, and (b) to devise a sequential test of GH reserve. DESIGN: The GH stimuli used were GHRH (1 microgram/kg i.v.) as a pituitary stimulus, and hexarelin (1 microgram/kg i.v.) as a GH stimulus whose main action is hypothalamic. Each subject was tested twice in order to serve as his own control. Three different studies, each with two duplicate tests, were performed on separate groups of individuals: (a) GHRH followed 120 minutes later by hexarelin and on the second day hexarelin followed 120 minutes later by GHRH; (b) GHRH followed 120 minutes later by GHRH and on the other day hexarelin followed 120 minutes later by hexarelin; (c) GH 0.5 IU i.v. followed 120 minutes later by GHRH and on the other day, the same dose of GH followed 120 minutes later by hexarelin. PATIENTS: Eighteen normal volunteers (12 women, 6 men) after giving informed consent. MEASUREMENTS: Plasma GH levels were measured by time-resolved fluoroimmunoassay; each value shown is the mean +/- SEM of n = 6. RESULTS: GHRH followed 120 minutes later by hexarelin induced two episodes of GH secretion (expressed as mean GH peak, mU/l). The GHRH-mediated GH release showed a mean GH peak of 38.2 +/- 13.6 mU/l and after hexarelin 120 minutes later of 56.7 +/- 18.0 mU/l. The contrary sequence blocked the second stimulus, i.e. the hexarelin-stimulated GH mean peak was 54.7 +/- 18.4, and the GH release 120 minutes later after GHRH was 4.8 +/- 1.9 (P < 0.05 vs GHRH used as first stimulus). In the two sequential tests using the same stimulus, the second GH peak was reduced. In fact, GHRH induced a GH mean peak of 63.8 +/- 21.1 mU/l as first stimulus, greater (P < 0.05) than when GHRH was administered again 120 minutes later (22.0 +/- 5.9 mU/l). Similar results were obtained with hexarelin, with a first mean peak of 70.6 +/- 10.3 mU/l, and a second one 120 minutes later of 13.4 +/- 4.6 mU/l (P < 0.05). The blockade of the second stimulus was not due to the feed-back action of the GH released by the first stimulus. In fact, the i.v. administration of exogenous GH induced a mean GH peak of 168.0 +/- 89.7 and reduced the action of GHRH administered 120 minutes later (26.1 +/- 8.1). The previous administration of GH (mean peak 115.5 +/- 42.0) did not alter the action of hexarelin injected 120 minutes later, showing a mean peak of 71.9 +/- 11.2. The large variability in the stimulatory action of GHRH contrasted vividly with the reproducibility of hexarelin. Furthermore, individually analysed, only one of the 12 subjects tested first with hexarelin, compared to 4 out of 12 tested with GHRH as first stimulus, presented a blunted response (< 13 mU/l). After the sequential stimulus there were no false negatives. CONCLUSION: The sequential administration of GHRH in normal subjects and of hexarelin 120 minutes later provides separate information regarding pituitary GH reserve, of both secretagogues without mutual interference. There were not false negative results to the combined test. This sequentially delayed test may be of some value in the clinical setting for assessing pituitary GH reserve.

Adult↗

PubMed1996

Growth hormone response to GHRH, GHRP-6 and GHRH + GHRP-6 in patients with polycystic ovary syndrome.

OBJECTIVE: Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non-classic GH secretagogues and, in particular, to the series of hexapeptides of which GH-releasing peptide (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, known as GHRP-6) is the most representative. GHRP-6 seems to be a promising tool for exploring GH secretory mechanisms and it has been reported that GHRH + GHRP-6 is a powerful stimulus to GH secretion. Our aim was to investigate the GH responses to GHRH, GHRP-6 and the administration of GHRP + GHRP-6 in two groups of patients (normal weight and obese) with PCOS in comparison with matched control groups. DESIGN: All subjects were studied three times on different days with GHRH (100 micrograms i.v.), GHRP-6 (90 micrograms i.v.) and GHRH + GHRP-6 (100 micrograms + 90 micrograms). PATIENTS: Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non-obese PCOS, n = 6, age 21.8 +/- 1.7 years, BMI 22.1 +/- 0.8 kg/m2); Group B: (obese PCOS, n = 10, age 21.7 +/- 1.3 years, BMI 32.9 +/- 2.1 kg/m2); Group C (non-obese healthy women, n = 13, age 26.8 +/- 1.5 years, BMI 21.8 +/- 0.6 kg/m2) and Group D (obese healthy women, n = 9, age 29.4 +/- 4.2 years, BMI 35.7 +/- 1.3 kg/m2). MEASUREMENTS: Serum GH was measured using a time-resolved fluoroimmunoassay (Delphia, Pharmacia). RESULTS: After GHRH administration significant differences were found between GH peaks in Groups A and B (82.4 +/- 16.4 vs 20 +/- 4.9 mU/l, P < 0.05) and in AUC for GH between Groups A and B (4667 +/- 1061 vs 947 +/- 236, P < 0.05) while there were no differences between the same groups in GH peak or AUC after GHRP-6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration of GHRH + GHRP-6 between Groups A and B (211 +/- 26.4 vs 108 +/- 17.6, P < 0.05) as well as between GH AUC in Groups A and B (12068 +/- 2323 vs 5997 +/- 1342, P < 0.05). There were no differences in GH peaks or AUC for GH after GHRH + GHRP-6 administration between Groups A and C or Groups B and D. CONCLUSIONS: The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesity and could be a functional defect, since it can be overridden with GHRP-6 administration.

Adult↗

PubMed1996

Serum immunoreactive-leptin levels are increased in patients with Cushing's syndrome.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Cushing's syndrome is a disease state usually associated with weight gain due to the accumulation of adipose tissue. In order to study the effect of chronic glucocorticoid excess upon serum leptin levels; in the present work, four patients with recently diagnosed Cushing's syndrome and a group of control subjects matched for age, sex and body mass index (BMI) were studied. Serum leptin concentrations, measured by radioimmunoassay, were assessed in samples taken every 60 minutes over a 24 hour period. Assessment of leptin concentrations over 24 hours, by means of the area under curve showed a twofold increase in serum leptin levels in patients with Cushing's syndrome (mean+/-SEM 54.3+/-14) in comparison to control subjects (29.3+/-4.4; p<0.05). In conclusion, our data show that leptin levels are markedly increased in Cushing's syndrome patients. The relevance of this finding to the increased body fat present in patients with Cushing's syndrome merits further studies.

Adult↗

PubMed1996

Regulation of growth hormone secretion.

The regulation of growth hormone (GH) secretion is complex, depending on the interaction of a wide array of central and peripheral feedback signals. In this brief review we will build up a picture of the current understanding of GH control mechanisms, highlighting areas of particular clinical relevance.

Animals↗

PubMed1996

Acipimox-mediated plasma free fatty acid depression per se stimulates growth hormone (GH) secretion in normal subjects and potentiates the response to other GH-releasing stimuli.

Increases in plasma free fatty acids (FFA) inhibit the GH response to a variety of stimuli; however, the role of FFA depression in GH control is far from understood. In the present work, FFA reduction was obtained by the administration to normal subjects of acipimox, a lipid-lowering drug devoid of side-effects. Each subject tested underwent two paired tests. In one, acipimox was administered orally at a dose of 250 mg at -270 min and at a dose of 250 mg at -60 min; in the matched test, placebo was given at similar intervals. To induce GH release, four stimuli acting through different mechanisms were used: pyridostigmine (120 mg, orally) at -60 min, GHRH (1 microgram/kg, iv) at 0 min, GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; 1 microgram/kg, iv) at 0 min, and finally, GHRH plus GHRP-6 at the same doses at 0 min. GH secretion was analyzed as the area under the secretory curve (AUC; mean +/- SE, micrograms per L/120 min). Acipimox pretreatment alone (n = 6) induced a reduction in FFA levels compared with placebo treatment. The FFA reduction led to a sustained GH secretion that increased from 2.4 +/- 1.8 micrograms/L at -120 min to 14.2 +/- 4.0 at 120 min. The GH AUC for placebo was 266 +/- 100, and that for acipimox was 1781 +/- 408 (P < 0.05). In the pyridostigmine-treated group (n = 6), the acipimox-pyridostigmine AUC (2046 +/- 323) was higher (P < 0.05) than the placebo-pyridostigmine AUC (764 +/- 101), but was not different from the AUC of acipimox alone. Previous FFA reduction nearly doubled the GHRH-mediated GH secretion (n = 6; placebo-GHRH AUC, 1817 +/- 365; acipimox-GHRH test, 3228 +/- 876; P < 0.05). A similar enhancement was observed when the stimulus employed was GHRP-6 (n = 6; placebo-GHRP-6 AUC, 2034 +/- 295; acipimox-GHRP-6, 4827 +/- 703; P < 0.05). Furthermore, even the most potent GH stimulus known to date, i.e. GHRH plus GHRP-6, was enhanced by the FFA suppression (placebo-GHRH-GHRP-6 AUC, 2034 +/- 277; acipimox-GHRH-GHRP-6, 5809 +/- 758; P < 0.05). The enhancing effect of lowering FFA levels was additive regardless of the stimulus employed. These results indicate that 1) FFA reduction per se stimulates GH secretion with a delayed time of action; 2) FFA reduction enhanced in an additive manner the GH secretion elicited by such different stimuli as pyridostigmine, GHRH, and GHRP-6; and 3) the observation that FFA reduction enhanced the response to the most potent GH stimulus, GHRH plus GHRP-6, suggests that FFA suppression acts by a separate mechanism. FFA reduction may have value in the clinical setting for assessing GH reserve.

Adolescent↗

PubMed1996

Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression.

GH secretion in response to provocative stimuli is blunted in obese patients. On the other hand, increases in plasma free fatty acids (FFA) inhibit the GH response to a variety of stimuli, and FFA levels in plasma are increased with obesity. To ascertain whether FFA might be responsible for the GH secretory alterations of obesity, we studied spontaneous and stimulated GH secretion in 31 obese patients after FFA reduction by acipimox, a lipid-lowering drug devoid of serious side-effects. Each subject underwent two paired tests. In one, acipimox was administered orally at a dose of 250 mg at -270 min and at a dose of 250 mg at -60 min; in the matched test, placebo was given at similar intervals. To induce GH release, three stimuli acting through different mechanisms were used: pyridostigmine (60 mg, orally, at -60 min), GHRH (100 micrograms, iv, at 0 min), and GHRH plus GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; both at a dose of 100 micrograms, iv, at 0 min). GH secretion was analyzed as the area under the secretory curve (AUC; mean +/- SE; micrograms per L/60 min). Acipimox pretreatment alone (n = 13) induced a large reduction in FFA levels compared with placebo treatment. The FFA reduction led to a slight GH rise (AUC, 123 +/- 47), not different from that in the placebo group (61 +/- 15). In the pyridostigmine-treated group (n = 6), the acipimox-pyridostigmine AUC (408 +/- 107) was significantly higher (P < 0.05) than that in the placebo-pyridostigmine group (191 +/- 25). Furthermore, the GHRH-mediated (n = 6) AUC of GH secretion in the placebo test (221 +/- 55) was tripled by FFA reduction due to acipimox, with an AUC of (691 +/- 134; P < 0.05). Even the most potent GH stimulus known to date, i.e. GHRH plus GHRP-6, was enhanced by FFA suppression. In fact, the placebo-GHRH-GHRP-6 AUC was 1591 +/- 349, lower (P < 0.05) than that in the acipimox-GHRH-GHRP-6 test (2373 +/- 242). The enhancing effects of FFA lowering on GHRH-mediated and GHRH- plus GHRP-6-mediated GH release were synergistic. These results indicate that in obese subjects, unlike normal weight subjects. FFA reduction per se does not stimulate GH secretion. A reduction in FFA with acipimox, however, increased pyridostigmine-. GHRH-, and even GHRH- plus GHRP-6-mediated GH release, suggesting that FFA reduction operates through a different mechanism from that of these three stimuli. The abnormally high FFA levels may be a contributing factor for the disrupted GH secretory mechanisms in obesity.

Adolescent↗

PubMed1996

Role of glucocorticoids in the neuroregulation of growth hormone secretion.

Elevated glucocorticoid (GC) levels produce a marked impairment in somatic growth in both rodents and primates. In addition, GC play an important role in the regulation of growth hormone (GH) synthesis and secretion. Blunted GH response to stimulation tests in conditions of chronic exposure to excessive cortisol secretion or administration are well documented. In contrast, acute administration of GC to normal human subjects induces a transient increase in plasma GH levels. This dual action of GC on GH secretion is probably due to the fact that they act at different loci; i.e. in the regulation of GH transcription and GHRH and somatostatin receptors at the pituitary level as well as GHRH, somatostatin and GH receptor gene expression at the hypothalamic level.

Animals↗