Growth hormone treatment for sustained pain reduction and improvement in quality of life in severe fibromyalgia.

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time.

Enfermedad celíaca del adulto: aspectos endocrinológicos y nutricionales / Adult celiac disease: endocrinological and nutritional issues

La enfermedad celíaca es una enteropatía autoinmune que aparece como respuesta a la ingesta de gluten en sujetos genéticamente predispuestos. Aunque históricamente se la ha considerado una patología pediátrica e infrecuente su prevalencia está próxima al 1% de la población general, siendo todavía más elevada en pacientes con determinadas patologías endocrinológicas y déficits nutricionales. El empleo de los anticuerpos antitransglutaminasa y antiendomisio y la endoscopia digestiva con toma de biopsia serán elementos clave para su diagnóstico. La instauración de una dieta sin gluten logrará la recuperación del trofismo intestinal y evitará el riesgo de complicaciones a largo plazo a la vez que mejora la calidad de vida del paciente. El seguimiento médico y nutricional será clave para lograr una buena adherencia terapéutica (AU)

Celiac disease is an autoinmune enterophaty induced by the ingestion of gluten in genetically susceptible individuals. Although historically it was thought that it was an infrequent pediatric disease, now it is know that its prevalence is close to 1% in the general population. It is even higher between patients with some endocrine disorders and nutritional deficits. The use of antitransglutaminase and antiendomisium antibodies and the endoscopical duodenal biopsy are the cornerstones for its diagnosis. The introduction of a gluten-free diet will achieve the normalization of the intestinal mucosa. It will avoid the risk of long term complications and an it will achieve an improvement in quality of life. Medical and dietitian long term follow-up will be important to improve the compliance to the treatment (AU)

[Adult celiac disease: endocrinological and nutritional issues]. / Enfermedad celíaca del adulto: aspectos endocrinológicos y nutricionales.

Celiac disease is an autoimmune enterophaty induced by the ingestion of gluten in genetically susceptible individuals. Although historically it was thought that it was an infrequent pediatric disease, now it is know that its prevalence is close to 1% in the general population. It is even higher between patients with some endocrine disorders and nutritional deficits. The use of antitransglutaminase and antiendomisium antibodies and the endoscopical duodenal biopsy are the cornerstones for its diagnosis. The introduction of a gluten-free diet will achieve the normalization of the intestinal mucosa. It will avoid the risk of long term complications and an it will achieve an improvement in quality of life. Medical and dietitian long term follow-up will be important to improve the compliance to the treatment.

A single growth hormone determination 30 minutes after the administration of the GHRH plus GHRP-6 test is sufficient for the diagnosis of somatotrope dysfunction in patients who have suffered traumatic brain injury.

UNLABELLED: As hypopituitarism is frequent in patients who have suffered a traumatic brain injury (TBI) a hormonal check-up is necessary. However, the prevalence of TBI is so large that the number of potential candidates to be tested is difficult to manage, in particular for GH deficiency diagnosis that requires cumbersome and expensive dynamic tests. GHRH plus GH-releasing hexapeptide (GHRP-6) is a safe and effective test capable of segregating normal subjects from GH deficient patients. As the GHRH+GHRP-6 test induces GH peaks consistently in the first 30 min, the working hypothesis assessed in this study was whether a single determination of GH 30 min after stimulus could provide the same biochemical classification as the whole secretory curve. A total of 83 subjects who suffered TBI at least one year before the study were administered GHRH 1 mug/kg iv plus GHRP-6 1 mug/kg iv at 0 min, and blood samples were obtained at regular intervals. GH was determined in all samples. An excellent correlation was observed between GH values at 30 min and GH peaks (r=0.972, p<0.0001). When comparing the 30-min GH values against the peaks, the biochemical classification changed only in 5 out of 83 subjects from normal GH secretion to uncertain. CONCLUSIONS: The GHRH+GHRP-6 test is convenient, safe and in patients with TBI can be reduced to a single fixed GH determination 30 min after stimulus without losing diagnostic power.

Can treatment with somatostatin analogs replace neurosurgery?

There is an ongoing controversy on first-line treatment in acromegaly. Although transsphenoidal surgery has always traditionally been considered the first option, the evolution of new medical treatments is now challenging the clinical paradigm. In fact, somatostatin analogs are highly effective, convenient, avoid the growth of tumors or even shrink them, and also have the advantage of preserving normal pituitary function. On the other hand, when successful, neurosurgery has the advantage of eliminating long-term medical treatment and is less expensive. This manuscript discusses the pros and cons of both treatments.

Therapeutic optimization of growth hormone deficiency in children and adolescents.

More than 40 years after the introduction of growth hormone (GH) treatment, many questions remain unanswered. Clearly, with the availability of rhGH and with current treatment protocols, treatment efficacy has improved. However, it still remains unclear whether current treatment protocols are the best possible. Before GH deficiency was recognized as a chronic disease, children only received treatment until normal adult height had been reached. However, it has recently been shown that not all GH-dependent body structures and functions normalize in parallel with height. Furthermore, in adolescents with GH deficiency, the interruption of GH substitution leads to severe hormone deficiency symptoms in adulthood. In the case of an adolescent who meets the biochemical criteria for GH deficiency in adulthood, but does not show alterations of metabolism, body structure, or emotional state, should GH treatment be started in adolescence, or only if and when the clinical syndrome becomes apparent? This is a difficult question to which there is not yet any clear answer, and we suggest that there is a need for further studies in this area. Furthermore, it will be necessary to re-evaluate the situation of patients who have completed their growth, and definitive conclusions will require controlled studies.

Optimización terapéutica del déficit de hormona de crecimiento en niños y adolescentes / No disponible

No disponible

TSH stimulates leptin secretion by a direct effect on adipocytes.

Leptin is a circulating hormone secreted by adipose tIssue which acts as a signal to the central nervous system where it regulates energy homeostasis and neuroendocrine processes. Although leptin modulates the secretion of several pituitary hormones, no information is available regarding a direct action of pituitary products on leptin release. However, it has been pointed out that leptin and TSH have a coordinated pulsatility in plasma. In order to test a direct action of TSH on in vitro leptin secretion, a systematic study of organ cultures of human omental adipose tIssue was performed in samples obtained at surgery from 34 patients of both sexes during elective abdominal surgery. TSH powerfully stimulated leptin secretion by human adipose tIssue in vitro. In contrast, prolactin, ACTH, FSH and LH were devoid of action. These results suggest that leptin and the thyroid axis maintain a complex and dual relationship and open the possibility that plasmatic changes in TSH may contribute to the regulation of leptin pulses.

Retinoic acid and vitamin D(3) powerfully inhibit in vitro leptin secretion by human adipose tissue.

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.

Ghrelin-induced growth hormone secretion in humans.

Ghrelin is a novel growth hormone (GH) releaser acylated peptide that has recently been purified from stomach, and which potently binds to the GH secretagogue receptor. Ghrelin releases GH in vitro and in vivo in animal models, however its actions, potency and specificity in humans are unknown. In the present study, 12 healthy subjects were studied: 6 underwent four tests with ghrelin administered i.v. at the dose of 0 (placebo), 0.25, 0.5 and 1 microg/kg which corresponds to 0, 18, 37 and 75 microg total dose. A further 6 volunteers underwent two tests on different days with ghrelin at the dose of 3.3 or 6.6 microg/kg which corresponds to 250 microg and 500 microg total dose. Ghrelin-mediated GH secretion showed a dose-response curve, in which 1 microg/kg was the minimally effective dose in some individuals, but not as a group. On the contrary, the total doses of 250 microg and 500 microg elicited a powerful GH secretion, with a mean peak of 69.8+/-9.2 microg/l and 90.9+/-16.9 microg/l respectively, and areas under the curve of 4435+/-608 and 6125+/-1008 microg/l per 120 min respectively. All of them statistically significant vs placebo and vs the 1 microg/kg dose. Ghrelin administration also elicited a relevant dose-response mediated prolactin secretion suggesting no specificity of its actions. No relevant side effects were observed with ghrelin apart from a hyperhydrosis episode in two individuals tested with the higher ghrelin doses. In conclusion, ghrelin is a potent releaser of GH in normal individuals, with a dose-response pattern of operation. No saturating dose was observed.

Cold exposure inhibits leptin secretion in vitro by a direct and non-specific action on adipose tissue.

OBJECTIVE: Leptin secretion is reduced by low temperatures in experimental animals, and this effect has been explained as an adaptive mechanism to cold environments. This study investigated the in vitro effects of cold exposure on human white adipose tissue. DESIGN: To understand whether the low temperature action is a direct or a mediated effect, leptin secretion was assessed in vitro in human omental adipose tissue incubated at varied temperatures, from 38 donors. As an internal control, the effect of reduced temperatures on in vitro GH secretion by GH3 cells was assessed. METHODS: Measurement of hormones secretion was carried out with an RIA, while human ob gene mRNA expression was assessed with reverse transcription PCR. RESULTS: Compared with the standard temperature of 37 degrees C, leptin secretion by human adipose tissue was significantly (P<0.05) reduced when the incubations were carried out at 34.5 degrees C (41% inhibition), and 32 degrees C (68% inhibition), with no parallel changes in the ob mRNA expression. At these reduced temperatures, glucocorticoid-mediated leptin secretion was well preserved. When the effect of reduced temperatures was assessed on in vitro GH secretion, a superimposable reduction was observed. CONCLUSIONS: These results indicate: (i) that low temperatures reduce leptin secretion by acting directly on the adipose tissue and (ii) that the similar reduction in a hormone unrelated to energy metabolism, such as GH, suggests that the observed reduction is a mechanical perturbation of leptin secretion, which may be devoid of physiological implications.

Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone.

Leptin, the product of the Ob gene, is a polypeptide hormone expressed in adipocytes which acts as a signalling factor from the adipose tissue to the central nervous system, regulating food intake and energy expenditure. It has been reported that circulating leptin levels are higher in women than in men, even after correction for body fat. This gender-based difference may be conditioned by differences in the levels of androgenic hormones. To explore this possibility, a systematic in vitro study with organ cultures from human omental adipose tissue, either stimulated or not with androgens (1 microM), was undertaken in samples obtained from surgery on 44 non-obese donors (21 women and 23 men). The assay was standardized in periods of 24 h, ending at 96 h, with no apparent tissue damage. Leptin results are expressed as the mean+/-s.e.m. of the integrated secretion into the medium, expressed as ng leptin/g tissue per 48 h. Spontaneous leptin secretion in samples from female donors (4149+/-301) was significantly higher (P<0.01) than that from male donors (2456+/-428). Testosterone did not exert any significant effect on in vitro leptin secretion in either gender (4856+/-366 in women, 3322+/-505 in men). Coincubation of adipose tissue with dihydrotestosterone (DHT) induced a significant (P<0.05) leptin decrease in samples taken from women (3119+/-322) but not in those taken from men (2042+/-430). Stanozolol, a non-aromatizable androgen, decreased (P<0.05) leptin secretion in female samples (2809+/-383) but not in male (1553+/-671). Dehydroepiandrosterone sulphate (DHEA-S) induced a significant (P<0.01) leptin decrease in female samples (2996+/-473), with no modifications in samples derived from males (1596+/-528). Exposure to androstenedione also resulted in a significant reduction (P<0.01) of leptin secretion in samples taken from women (2231+/-264), with no effect on male adipose tissue (1605+/-544). In conclusion, DHT, stanozolol, DHEA-S and androstenedione induced a significant inhibition of in vitro leptin secretion in samples from female donors, without affecting the secretion in samples from men. Testosterone was devoid of activity in either gender.

Effect of resistance exercise (body building) training on serum leptin levels in young men. Implications for relationship between body mass index and serum leptin.

UNLABELLED: Available data about the influence of exercise on leptin level are controversial, and there are no studies concerning leptin levels in trained men with low fat mass plus large increase of muscle. 65 healthy young male matched for age were separated in three groups. 1) 25 non-professional body builders; 2) 21 mild overweight sedentary subjects; 3) 19 normal weight sedentary controls. Body composition was determined by bioelectrical impedance. Serum leptin was measured in duplicate by RIA. STATISTICS: Student's t and Pearson's test. Athletes showed similar BMI than overweight subjects: 26.98+/-0.49 vs 27.12+/-0.41 but lower fat mass: 12.53+/-0.96 vs 16.16+/-1.01 % (p=0.0064) and lower leptin: 4.66+/-0.51 vs 7.31+/-0.76 microg/l (p=0.014). Athletes showed higher BMI than controls: 26.98+/-0.49 vs 23.08+/-0.30 (p<0.0001) but similar fat mass: 12.53+/-0.96 vs 12.48+/-0.73% and leptin: 4.66+/-0.51 vs 4.79+0.58 microg/l. Overweight subjects showed higher BMI than controls: 27.12+/-0.41 vs 23.08+/-0.30 (p<0.0001), higher fat mass: 16.16+/-1.01 vs 12.48+/-0.73% (p=0.0064) and higher leptin: 7.31+/-0.76 vs 4.79+/-0.589 microg/l (p=0.014). When leptin was calculated by fat mass no differences were observed between the three groups. There was a significant correlation between leptin and fat mass in all groups. Leptin correlated with BMI in overweight subjects (r=0.438, p=0.0463), but this correlation was not observed either in athletes or in controls. In conclusion 1) regardless of the high BMI characteristic of body builders, no correlation was observed with leptin; 2) trained state induced by resistance exercise does not influence leptin production independently of variations in body composition.

Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism.

In obesity, there is a markedly decreased GH secretion. The diagnosis of GH deficiency (GHD) in adults is based on peak GH responses to stimulation tests. In the severely obese, peak GH levels after pharmacological stimulation are often in the range that is observed in hypopituitary patients. To distinguish obese subjects from GHD patients, it will be necessary to demonstrate that reduced GH responsiveness to a given test is reversible in the former, but not in the latter, group. Recent studies have shown that reduction of plasma free fatty acids (FFA) with acipimox in obese patients restores their somatotrope responsiveness. There are no data evaluating GH responsiveness to acipimox plus GHRH in obese adults with hypopituitarism. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on GHRH-mediated GH secretion in obese normal subjects and obese adults with hypopituitarism. Eight obese patients with a body mass index of 34.2+/-1.2; eight obese adults with hypopituitarism, with a body mass index of 35.5+/-1.9; and six control subjects were studied. All the patients showed an impaired response to an insulin-tolerance test (0.15 U/kg, i.v.), with a peak GH secretion of less than 3 microg/L. Two tests were carried out. On one day, they were given GHRH (100 microg, i.v., 0 min), preceded by placebo; and blood samples were taken every 15 min for 60 min. On the second day, they were given GHRH (100 microg, i.v., 0 min), preceded by acipimox (250 mg, orally, at -270 min and -60 min); and blood samples were taken every 15 min for 60 min. The administration of acipimox induced a FFA reduction during the entire test. Normal control subjects had a mean peak (microg/L) of 23.8+/-4.8 after GHRH-induced GH secretion; previous acipimox administration increased GHRH-induced GH secretion, with a mean peak of 54.7+/-14.5. In obese patients, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 3.9+/-1; previous administration of acipimox markedly increased GHRH-mediated GH secretion, with a mean peak of 16.0+/-3.2 (P < 0.05). In obese adults with hypopituitarism, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 2+/-0.7; previous acipimox administration did not significantly modify GHRH-mediated GH secretion, with a mean peak of 3.3+/-1.1 (P < 0.05). The GH response of obese patients and obese adults with hypopituitarism was similar after GHRH alone. In contrast, the GH response after GHRH plus acipimox, was markedly decreased in obese adults with hypopituitarism (mean peak, 3.3+/-1.1), compared with obese patients (mean peak, 16.0+/-3.2) (P < 0.05) and control subjects (mean peak, 54.7+/-14.5) (P < 0.01). In conclusion, GH secretion, after GHRH-plus-acipimox administration, is reduced in obese adults with hypopituitarism patients, when compared with obese normal patients. Testing with GHRH plus acipimox is safe and is free from side effects and could be used for the diagnosis of GHD in adults.

PMA inhibits both spontaneous and glucocorticoid-mediated leptin secretion by human omental adipose tissue explants in vitro.

The activation of PKC by the acute administration of the phorbol ester PMA (1 microM, 2h) to omental adipose tissue explants in vitro resulted in a marked (about 75%) and persistent (up to at least 96 h) inhibition of leptin secretion. This PKC-mediated inhibition was not observed after the administration of an inactive phorbol ester (phorbol 12,13-dicecanoate). The inhibition by PMA of leptin secretion was not restricted to the spontaneous secretion, but blocked also effectively the leptin response to a powerful stimulus, such as the glucocorticoid dexamethasone. As the PKC activity has been shown to be elevated during fasting, the negative relation here described between PKC activity and leptin secretion could be of physiological relevance.

Acute changes in free-fatty acids (FFA) do not alter serum 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 changes in circulating free-fatty acids on serum leptin levels. Increases in plasma FFA levels (p < 0.02) were obtained in a group of normal subjects following the administration of intralipid plus heparin (250 ml 10% Intralipid plus 5000 U heparin). FFA reduction was achieved through the administration of acipimox (250 mg, orally, at 0 min and at 210 min), a lipid-lowering drug devoid of side effects, to a group of normal (p < 0.02) and obese subjects (p < 0.05). An increase in circulating FFA levels in normal subjects (n = 6), following administration of a lipid-heparin infusion, failed to modify plasma leptin levels as assessed by the area under the curve (AUC; mean +/- SE 892 +/- 168 for placebo vs 896 +/- 260 following intralipid plus heparin). Similarly, whereas acipimox pretreatment induced a reduction in FFA levels compared to placebo in normal (n = 6) and obese subjects (n = 8), it also failed to modify plasma leptin levels at any time-point studied. The results indicate that short-term reduction or increase in circulating FFA are not associated to changes in plasma leptin levels.

Serum leptin levels in male marathon athletes before and after the marathon run.

Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. It is commonly accepted that the main determinants of leptin secretion are the net amount of body fat and the mean size of adipocytes. On the contrary, important vectors of energy flux in the organism, such as food intake and energy expended on exercise, are not thought to be regulators of that secretion. To understand whether leptin is regulated by an acute energy expenditure such as strenuous exercise, 29 male athletes who had trained for marathon running were studied before and after a marathon run and compared with 22 nonobese, age-, sex-, and body mass index (BMI)-matched sedentary controls. Controls and marathon athletes showed no differences in BMI or fat-free mass. Marathon runners showed a strong reduction in total fat mass (6.2 +/- 0.4 kg; 9.1 +/- 0.5% of body fat) compared with controls (12.3 +/- 0.5 kg; 16.1 +/- 0.5% of body fat; P < 0.05). This difference in body composition was paralleled by a mean serum leptin level that in marathonians (2.9 +/- 0.2 micrograms/L) was significantly (P < 0.05) reduced compared with that in controls (5.1 +/- 0.6 micrograms/L). It is remarkable that the ratio of leptin per kg body fat, showed a very good agreement between the two groups, 0.40 +/- 0.04 microgram/L.kg for controls and 0.46 +/- 0.03 microgram/L.kg for marathonians. In the two groups, leptin was correlated with both body weight, BMI, and fat mass (P < 0.001). The marathon trajectory was the standard 42.195 km accomplished in an average time of 3 h, 17 min, 7 s, with a calculated energy expenditure of over 2800 Cal. After the marathon run, a water imbalance occurred, with a significant decrease in body weight and an increase in serum albumin. A significant (P < 0.05) reduction in leptin values was observed after the run (2.6 +/- 0.2 micrograms/L) compared with before (2.9 +/- 0.2 micrograms/L), which was more relevant considering the relative hemoconcentration. In conclusion, 1) compared with sedentary subjects, leptin levels are reduced in male marathon runners in parallel with the relevant reduction in total body fat; 2) expressed as a ratio of leptin per kg body fat, no differences were observed between marathonians and controls; and 3) after an energy expenditure of 2800 Cal in the marathon run, a reduction in leptin levels occurred. Strong changes in energy expenditure may regulate serum leptin levels in man.

Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: dexamethasone and estradiol stimulate leptin release in women, but not in men.

Leptin is a hormone secreted by the adipocytes to serve as a signal to the central nervous system to regulate energy homeostasis. Circulating leptin mainly reflects both total fat mass and the size of constituent adipocytes, although other ancillary hormonal factors may contribute to its blood concentration. Relevant gender differences in leptin concentrations have been reported, but it is not clear whether the elevated leptin levels in women are an intrinsic property of their adipocytes or merely reflect a greater amount of fat reserves. To clarify these points, a systematic study with organ culture from human omental adipose tissue either stimulated or not with steroid hormones was undertaken in samples obtained at surgery from 67 nonobese donors (33 women and 34 men). The assay was standardized in periods of 24 h ending at 96 h, with no apparent tissue damage. Each adipose tissue sample from a single donor was incubated in triplicate, and leptin results are expressed as the mean +/- SEM of the integrated secretion to the medium (area under the curve; nanograms of leptin per g tissue/48 h). Control nonstimulated samples showed a steady leptin secretion along the 96 h studied, with the peak of secretory activity reached at 48 h; afterward, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in samples from 33 women (3904 +/- 347) was significantly higher (P < 0.05) than that in samples from 34 men (2940 +/- 323). Coincubation of adipose tissue with 1 mumol/L dexamethasone induced a clear-cut leptin increase (P < 0.05) in samples from women (5848 +/- 624; n = 12), but did not change the spontaneous release of leptin in samples from men (3353 +/- 741; n = 6). Similarly, coincubation of adipose tissue with 1 mumol/L estradiol induced a notable leptin increase (P < 0.05) in samples from women (5698 +/- 688; n = 9), whereas it did not alter the secretion in the male samples (3373 +/- 444; n = 6). In samples from both sexes, coincubation with 1 mumol/L estrone or progesterone had no effect, whereas 1 mumol/L forskolin significantly (P < 0.05) reduced leptin release. In conclusion, leptin secretion from omental adipose tissue in vitro 1) is significantly higher in samples from women than in samples from men, 2) is stimulated by dexamethasone and estradiol in women but not in men, 3) is not modified by progesterone or estrone in both sexes, and 4) is inhibited by forskolin in both genders. This different response to the stimulation of adipose tissue may be the biological basis for the gender differences observed in circulating levels of human leptin.

Neuropharmacological assessment of growth hormone secretion.

The biochemical diagnosis of individuals who are either deficient in growth hormone (GH) or who have alterations in the normal pattern of GH secretion is difficult. The uncertainty surrounding diagnosis reflects the lack of a thorough understanding of the physiology of GH secretion and of the hypothalamic hormones involved. At least three hormones are implicated: GH-releasing hormone (GHRH), somatostatin and the endogenous ligand of the GH secretagogue receptor, although the role that each plays in the release of GH is not clear from the available experimental evidence. In such a situation, most of the dynamic tests of GH secretory capacity in humans need to undergo a 'trial and error' process before being validated. The search for the 'gold standard' test of GH secretion is ongoing, and the combination of GHRH plus GH secretagogues will probably play an important role in future clinical diagnosis.