help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tannenbaum, G. S.
Right arrow Articles by Lapointe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tannenbaum, G. S.
Right arrow Articles by Lapointe, M.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Endocrinology Vol. 139, No. 9 3871-3875
Copyright © 1998 by The Endocrine Society

ARTICLES

Leptin Is a Potent Stimulator of Spontaneous Pulsatile Growth Hormone (GH) Secretion and the GH Response to GH-Releasing Hormone1

Gloria Shaffer Tannenbaum2, Wendy Gurd and Martine Lapointe

Departments of Pediatrics, and Neurology and Neurosurgery, McGill University; and the Neuropeptide Physiology Laboratory, McGill University-Montreal Children’s Hospital Research Institute, Montreal, Québec, Canada H3H 1P3

Address all correspondence and requests for reprints to: Dr. Gloria S. Tannenbaum, Neuropeptide Physiology Laboratory, McGill University-Montreal Children’s Hospital Research Institute, 2300 Tupper Street, Montreal, Québec, Canada H3H 1P3. E-mail: mcta{at}musica.mcgill.ca


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Pulsatile GH secretion is exquisitely sensitive to perturbations in nutritional status, but the underlying mechanisms are largely unknown. Leptin, a recently discovered adipose cell hormone, is thought to be a sensor of energy stores and to regulate body mass, appetite, and metabolism at the level of the brain. Receptors for leptin are abundantly expressed in hypothalamic nuclei known to be involved in GH regulation, suggesting that leptin may serve as an important hormonal signal to the GH neuroendocrine axis in normal animals. To test this hypothesis, we examined the effects of intracerebroventricular infusion of recombinant murine leptin, at a dose of 1.2 µg/day for 7 days, on both spontaneous and GH-releasing hormone (GHRH)- stimulated GH secretion in free-moving adult male rats. Concomitant with suppressive effects on food intake, body weight, and basal plasma insulin-like growth factor I, insulin, and glucose concentrations, central infusion of leptin resulted in a 2- to 3-fold augmentation of GH pulse amplitude, 5-fold higher GH nadir levels, and a 2- to 3-fold increase in the integrated area under the 6-h GH response curve compared with those in vehicle-infused controls (P < 0.001). The intracerebroventricular infusion of leptin also produced a 3- to 4-fold increase in GHRH-induced GH release at GH trough times (P < 0.01). These studies demonstrate a potent stimulatory action of leptin on both spontaneous pulsatile GH secretion and the GH response to GHRH. The results suggest that the GH-releasing activity of leptin is mediated, at least in part, by an inhibition of hypothalamic somatostatin release. Thus, leptin may be a critical hormonal signal of nutritional status in the neuroendocrine regulation of pulsatile GH secretion.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
THE GH neuroendocrine axis is exquisitely sensitive to changes in nutritional status. Spontaneous pulses of GH release are markedly suppressed in response to a whole host of metabolic perturbations, including food deprivation, insulinopenic diabetes, and intracellular glucopenia (see Ref. 1 for review). Furthermore, obesity is associated with an impairment of both spontaneous and GH-releasing hormone (GHRH)-induced GH secretion in both humans (2) and experimental animal models (3, 4). This hyposomatotropism probably results in decreased lipolysis (5) and may serve to perpetuate the underlying obese state. However, the mechanisms by which metabolic and nutritional factors contribute to the neuroendocrine regulation of GH secretion are largely unknown.

One such possible regulator is leptin, the recently discovered adipose cell hormone that is the protein product of the ob gene (6). Leptin is secreted from adipocytes and is thought to be a sensor of energy stores and to regulate appetite and metabolism at the level of the brain (7, 8). Indeed, blood concentrations of leptin increase during times of caloric repletion and decrease during fasting (9). Rapidly accumulating data have implicated leptin as a humoral link between nutrition and several neuroendocrine systems (10, 11, 12, 13).

The discovery of leptin receptor expression in the brain (14) lends credence to this hypothesis. In fact, receptors for leptin are abundantly expressed in those hypothalamic nuclei known to be involved in GH regulation, including the arcuate and periventricular nuclei (15, 16), and systemic injection of leptin induces Fos protein in the arcuate nucleus (17). Recent double labeling studies have shown the presence of leptin receptor immunoreactivity in arcuate GHRH-containing neurons (18). These observations suggest that leptin may serve as an important hormonal signal in the regulation of pulsatile GH secretion.

To test this hypothesis, we examined the effects of intracerebroventricular (icv) infusion of leptin on both spontaneous and GHRH-stimulated GH secretion in normal free-moving rats. Food intake, body weight, and plasma concentrations of insulin-like growth factor I (IGF-I), insulin, and glucose were also monitored.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals and experimental procedure
Adult male Sprague-Dawley rats (225–300 g) were purchased from Charles River Canada (St. Constant, Canada) and individually housed on a 12-h light, 12-h dark cycle (lights on, 0600–1800 h) in a temperature (22 ± 1 C)- and humidity-controlled room. Purina rat chow (Ralston-Purina, St. Louis, MO) and tap water were available ad libitum. Chronic icv and intracardiac venous cannulas were implanted under sodium pentobarbitol (50 mg/kg, ip) anesthesia using previously described techniques (19, 20). The placement of the icv cannula was verified by both a positive drinking response to carbachol (100 ng/10 µl) icv injection on the day after surgery and methylene blue dye at the time of death. After surgery, the rats were placed directly in isolation test chambers with food and H2O freely available until body weight returned to preoperative levels (usually within 5–7 days). They were then implanted sc on the dorsum, under local lidocaine 1% anesthesia, with osmotic minipumps (Alzet 2001, Alza Corp., Palo Alto, CA) containing either recombinant murine leptin (Amgen, Thousand Oaks, CA; 1.2 µg/day over 7 days) or the phosphate-buffered saline (PBS) vehicle. The icv cannula was connected to the minipump by means of a brain infusion kit (Alzet 3–5 mm, Alza Corp.). During the 7-day period of continuous infusion, 24-h food intake and body weight were monitored daily. Food consumption was calculated by subtracting uneaten food plus spillage from the total given. On the test day, food was removed 1.5 h before the start of sampling and was returned at the end. Leptin or vehicle infusion was maintained during the sampling periods.

In the first experiment, we documented the effects of icv infusion (6–7 days) of either leptin (n = 7) or PBS (n = 7) on spontaneous pulsatile GH release in free-moving rats. Blood samples (0.4 ml) were withdrawn every 15 min over a 6-h sampling period (1000–1600 h) from all animals. All blood samples were immediately centrifuged, and the plasma was separated and stored at -20 C for subsequent assay of GH, IGF-I, insulin and glucose. To avoid hemodynamic disturbance, the red blood cells were resuspended in normal saline and returned to the animal after removal of the next blood sample.

In the second experiment, we assessed the effects of centrally infused leptin (6–7 days) on GH responsiveness to GHRH. Free-moving, chronically cannulated rats, implanted with osmotic minipumps as described above, were administered 1 µg rat GRF-(1–29)NH2iv at two different time points during the 6-h sampling periods. The times of 1100 and 1300 h were chosen because these times reflect typical peak and trough periods of GH secretion, as previously documented (19, 21). The GHRH peptide (provided by Dr. P. Brazeau, Notre Dame Hospital, Montreal, Canada) was diluted in normal saline just before use. To document the rapidity of the GH response to GHRH, an additional blood sample was obtained 5 min after each injection of the peptide. All animal-based procedures were approved by the McGill University Animal Care Committee.

Hormone assays
Plasma GH concentrations were measured in duplicate by double antibody RIA using materials supplied by the NIDDK Hormone Distribution Program (Bethesda, MD). The averaged plasma GH values are reported in terms of the rat GH reference preparation (rGH RP-2). The standard curve was linear between 0.62–320 ng/ml; the least detectable concentration of plasma GH under the conditions used was 1.2 ng/ml. The intra- and interassay coefficients of variation were 7.7% and 10.7%, respectively, for duplicate samples of pooled plasma containing a mean GH concentration of 60.7 ng/ml.

Plasma IGF-I concentrations were measured using a previously described method (22). To decrease the interference of IGF-binding proteins in the assay, the samples were prepared by acid-ethanol extraction followed by cryoprecipitation. The IGF-I/somatomedin C rabbit antiserum (UB3–189) was obtained from the NIDDK Hormone Distribution Program (gift from Drs. L. Underwood and J. Van Wyk). Recombinant human IGF-I (Eli Lilly Co., Indianapolis, IN) was iodinated by the chloramine-T method. The averaged plasma IGF-I values are reported in terms of the recombinant human IGF-I reference preparation (Eli Lilly Co.). The standard curve was linear between 0.1–25 ng/ml. The intra- and interassay coefficients of variation were 4.8% and 14.8%, respectively, for duplicate samples of pooled plasma containing a mean IGF-I concentration of 0.82 ng/ml.

Plasma insulin was measured by a dextran-coated charcoal method using guinea pig antiporcine insulin serum (23). Purified crystalline rat insulin (lot 615-JE 6-9, Eli Lilly Co., provided by Dr. R. Chance) served as a reference standard. The sensitivity of the assay was 0.16 ng/ml, and the intra- and interassay coefficients of variation were 8.2% and 10.3%, respectively, for duplicate samples of pooled plasma containing a mean plasma insulin concentration of 5.68 ng/ml. Plasma glucose was measured by an automated glucose oxidase method (Glucose Analyzer 2, Beckman Instruments, Palo Alto, CA).

Statistical analyses
The plasma GH profiles of individual rats were analyzed using the Cluster Analysis Program for endocrine pulse detection (24). Briefly, a t statistic of 2.0 was selected to maintain a maximal false positive rate of 2.5% or less, using test cluster sizes of 2 in the prepeak nadir, peak, and postpeak nadir. Student’s t tests for unpaired and paired data, as appropriate, were used for statistical comparisons between and within experimental groups. The integrated area under the GH response curve (AUC) was calculated by the linear trapezoidal method. The results are expressed as the mean ± SE. P < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Effects of icv infusion of leptin on daily food intake and body weight gain
The adequacy of icv leptin administration was confirmed by observing the effects on daily food intake and body weight gain (Fig. 1Go). While PBS-infused rats gained 25.4 ± 7.8 g after 7 days, leptin-treated animals lost 19.2 ± 7.6 g during the same time period. Mean daily food intake in leptin-infused rats was significantly suppressed by 24 h after the onset of infusion and remained significantly reduced (~38%) throughout the 7-day observation period compared with that in PBS-treated controls (Fig. 1Go).



View larger version (19K):
[in this window]
[in a new window]
  		Figure 1. Effects of central infusion of leptin on daily body weight gain and food intake. Values are the mean ± SE; the number of animals in each group is shown in parentheses; the arrow indicates the time of osmotic minipump implantation. *, P < 0.01 or less compared with PBS-treated controls.

 
Effects of centrally infused leptin on spontaneous pulsatile GH release
As shown in Fig. 2AGo, PBS icv-infused control rats exhibited the typical pulsatile pattern of GH secretion. Two major episodes of GH release were evident during the 6-h sampling period, with most peak GH values greater than 125 ng/ml; in the intervening trough periods, basal plasma GH levels were mostly undetectable.



View larger version (24K):
[in this window]
[in a new window]
  		Figure 2. Individual representative 6-h plasma GH profiles in two PBS icv-infused control rats (A) compared with those in rats administered leptin (1.2 µg/day over 7 days) icv (B). Central infusion of leptin resulted in a marked stimulation of the spontaneous GH secretory episodes. The number in parentheses is a data point off the scale of the figure.

 
Central infusion of leptin resulted in a marked stimulation of the spontaneous GH secretory episodes (Fig. 2BGo); in some rats, the amplitude of the GH peaks reached values as high as 700 ng/ml. Cluster analysis of GH pulse parameters showed that leptin-infused rats exhibited a 2- to 3-fold augmentation of GH peak amplitude, approximately 5-fold higher GH nadir levels, and a 2- to 3-fold increase in the 6-h GH AUC (P < 0.001) compared with those parameters in vehicle-infused controls (Fig. 3Go). Neither the GH peak frequency (3.1 ± 0.5 vs. 2.3 ± 0.2), interpeak interval (105.0 ± 17.3 vs. 139.3 ± 19.3 min), or peak width (91.2 ± 17.9 vs. 113.6 ± 8.6 min) were significantly altered. Basal plasma IGF-I, insulin, and glucose concentrations were all significantly reduced in leptin-infused rats compared with those in PBS-treated controls (Table 1Go).



View larger version (20K):
[in this window]
[in a new window]
  		Figure 3. Cluster analysis of the effects of centrally infused leptin on GH pulse parameters. Each bar represents the mean ± SE; the number of animals in each group is shown in parentheses. a, P < 0.05 or less compared with PBS-infused controls.

 

View this table:
[in this window]
[in a new window]
  		Table 1. Effects of intracerebroventricular infusion of leptin on basal plasma IGF-I, insulin, and glucose levels

 
Effects of centrally infused leptin on GH responsiveness to GHRH
Figure 4Go illustrates the mean plasma GH response to GHRH in animals infused with either PBS or leptin for 6–7 days and then challenged with GHRH. As shown in Fig. 4AGo, PBS-treated controls exhibited the typical intermittent male pattern of GH responsiveness to GHRH (21), with high GHRH-induced GH release observed when GHRH was injected at peak times (1100 h) and only a limited response during GH trough periods (1300 h). The magnitude of the GH response to GHRH at 1100 h was significantly greater than that at 1300 h (P < 0.01). In contrast, pretreatment with leptin abolished this time-dependent difference and resulted in a marked augmentation (3- to 4-fold) of GHRH-induced GH release at 1300 h compared with that in PBS-infused controls (30 min GH AUC, 166.6 ± 27.0 vs. 38.7 ± 12.5 ng/ml·h; P < 0.01; Fig. 4BGo). Leptin-treated rats also exhibited a higher GH response to GHRH at 1100 h, although this difference did not reach significance (30 min GH AUC, 185.1 ± 24.3 vs. 162.7 ± 16.6 ng/ml·h). Of interest, GH trough levels in the leptin-treated animals rarely reached undetectable levels, in contrast to those in PBS-treated controls (see Fig. 4Go).



View larger version (23K):
[in this window]
[in a new window]
  		Figure 4. Mean plasma GH response to 1 µg GHRH iv administered at 1100 and 1300 h in rats infused icv with either the PBS vehicle (A) or leptin (1.2 µg/day over 7 days; B). Pretreatment with leptin resulted in a marked augmentation of GHRH-induced GH release at 1300 h compared with that in PBS-infused controls. Also note elevation of GH trough levels in leptin-treated rats. Vertical lines represent the SE; the number of animals in each group is shown in parentheses.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
These studies clearly demonstrate that leptin exerts potent stimulatory actions on both spontaneous pulsatile GH secretion and the GH response to GHRH. The results suggest that leptin may be an important positive regulator of GH pulsatility in normal animals.

The present findings are congruent with accumulating data implicating leptin as a humoral link between nutrition and several endocrine systems, including the gonadal, adrenal, and thyroid axes (10, 11, 12). They are also in conformity with an earlier report in the rat demonstrating that icv administered leptin antiserum resulted in a decrease in spontaneous GH release (13) and with a recent study in pigs showing leptin stimulation of GH (25). Together these findings provide support for the thesis that leptin may be a critical hormonal signal of nutritional status to the GH neuroendocrine axis.

The dramatic enhancement of GH pulsatility observed in the present study (i.e. 2- to 3-fold above the normal high amplitude GH pulses of control rats) was all the more remarkable given the sustained anorexia induced by centrally administered leptin, since previous studies in the rat have consistently found GH to be markedly suppressed in nutritionally deprived states (1, 22, 23). If leptin is a stimulatory signal to the GH neuroendocrine axis, a fall in circulating leptin concentrations might translate into lower GH pulses. Indeed, the observation that blood levels of leptin are significantly decreased during fasting (10) is consistent with this idea.

The leptin-induced reductions in plasma concentrations of insulin, glucose, and IGF-I reported here are in agreement with the results of previous studies (26, 27). Although leptin may exert direct effects on one or more of these parameters (28), it is also possible that these responses are secondary to the reduction in food intake we observed, as plasma IGF-I, insulin, and glucose are known to be impaired in poorly nourished animals (10, 22, 23). On the other hand, as increases in GH levels are not normally seen in nutritionally deprived states in the rat, the increases in GH observed in these experiments are probably a result of the administered leptin rather than of changes in nutritional status.

The mechanism(s) by which leptin influences pulsatile GH secretion is of interest. Current experimental evidence indicates that the pulses of GH secretion are due to the episodic release of hypothalamic GHRH, whereas somatostatin (SRIF) is the physiological regulator of GH trough periods (29). The present finding of a 5-fold increase in GH nadir levels in leptin-infused animals suggests that SRIF may be involved in this response. Support for this concept was obtained in our GHRH challenge experiments; pretreatment with leptin reversed the weak GH response to GHRH observed in PBS-infused controls at GH trough times, the latter known to be due to antagonization by the increased cyclical release of endogenous SRIF (21). These results, therefore, suggest that the GH-releasing activity of leptin is mediated at least in part by inhibiting hypothalamic SRIF release into hypophyseal portal blood. This interpretation would be in keeping with the recent in vitro demonstration that leptin inhibits SRIF synthesis and secretion in cultured fetal rat neurons (30).

Furthermore, it is also possible that a reduction of SRIF tone within the hypothalamus contributed to the leptin-induced augmentation in GH pulse amplitude, as SRIF may directly regulate GHRH release at the level of the arcuate nucleus (29). Alternatively, GHRH secretion may be a target for regulation by leptin, because GHRH neurons harbor leptin receptors (18), and hypothalamic GHRH is altered both in response to fasting (31) and in the genetically obese Zucker rat (4, 32). Finally, the GH stimulatory actions of leptin may be mediated indirectly via interactions with other neuronal pathways known to be both responsive to leptin and to influence GH, such as the neuropeptide Y and CRH neuroendocrine systems (16, 33, 34). Additional studies will be required to identify the complete neuroendocrine pathways through which leptin stimulates GH secretion.


   Acknowledgments
 
We thank Drs Jeffrey Friedman and Jeffrey Halaas for stimulating discussion and the gift of leptin. We are grateful to Dr. R. Chance for the gift of rat insulin, to the NIDDK for the provision of GH and IGF-I RIA materials, and to Julie Temko for preparation of the manuscript.


   Footnotes
 
1 This work was supported by Grant MT-6837 (to G.S.T.) from the Medical Research Council of Canada. Back

2 Chercheur de Carrière of the Fonds de la Recherche en Santé du Québec. Back

Received March 25, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Tannenbaum GS 1987 Physiological significance of somatostatin in growth hormone regulation. In: Reichlin S (ed) Somatostatin: Basic and Clinical Status. Plenum Press, New York, pp 169–182
  2. Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier J, Vale W, Frohman LA 1984 Impaired growth hormone responses to growth hormone-releasing factor in obesity: a pituitary defect reversed with weight reduction. N Engl J Med 311:1403–1407[Abstract]
  3. Finkelstein JA, Jervois P, Menadue M, Willoughby JO 1986 Growth hormone and prolactin secretion in genetically obese Zucker rats. Endocrinology 118:1233–1236[Abstract]
  4. Tannenbaum GS, Lapointe M, Gurd W, Finkelstein JA 1990 Mechanisms of impaired growth hormone secretion in genetically obese Zucker rats: roles of growth hormone-releasing factor and somatostatin. Endocrinology 127:3087–3095[Abstract]
  5. Scanes CG 1996 Growth hormone actions: lipid metabolism. In: Harvey S, Scanes CG, Daughaday W (eds) Growth Hormone. CRC Press, Boca Raton, pp 379–387
  6. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM 1994 Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432[CrossRef][Medline]
  7. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM 1995 Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546[Abstract/Free Full Text]
  8. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P 1995 Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546–549[Abstract/Free Full Text]
  9. Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV 1996 Leptin: the tale of an obesity gene. Diabetes 45:1455–1462[Medline]
  10. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS 1996 Role of leptin in the neuroendocrine response to fasting. Nature 382:250–252[CrossRef][Medline]
  11. Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, Clifton DK, Steiner RA 1996 Leptin is a metabolic signal to the reproductive system. Endocrinology 137:3144–3147[Abstract]
  12. Yu WH, Kimura M, Walczewska A, Karanth S, McCann SM 1997 Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA 94:1023–1028[Abstract/Free Full Text]
  13. Carro E, Señaris R, Considine RV, Casanueva FF, Dieguez C 1997 Regulation of in vivo growth hormone secretion by leptin. Endocrinology 138:2203–2206[Abstract/Free Full Text]
  14. Tartaglia L, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Woolf EA, Monroe CA, Tepper RI 1995 Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263–1271[CrossRef][Medline]
  15. Mercer JG, Hoggard N, Williams LM, Lawrence CB, Hannah LT, Trayhurn P 1996 Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett 387:113–116[CrossRef][Medline]
  16. Schwartz MW, Seeley RJ, Campfield LA, Burn P, Baskin D 1996 Identification of targets of leptin action in rat hypothalamus. J Clin Invest 98:1101–1106[Medline]
  17. Woods AJ, Stock MJ 1996 Leptin activation in hypothalamus. Nature 381:745[Medline]
  18. Håkansson M-L, Brown H, Ghilardi N, Skoda RC, Meister B 1998 Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 18:559–572[Abstract/Free Full Text]
  19. Tannenbaum GS, Martin JB 1976 Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology 98:562–570[Abstract]
  20. Tannenbaum GS 1980 Evidence for autoregulation of growth hormone secretion via the central nervous system. Endocrinology 107:2117–2120[Abstract]
  21. Tannenbaum GS, Ling N 1984 The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 115:1952–1957[Abstract]
  22. Harel Z, Tannenbaum GS 1995 Long-term alterations in growth hormone and insulin secretion after temporary dietary protein restriction in early life in the rat. Pediatr Res 38:747–753[Medline]
  23. Tannenbaum GS, Epelbaum J, Colle E, Brazeau P, Martin JB 1978 Antiserum to somatostatin reverses starvation-induced inhibition of growth hormone but not insulin secretion. Endocrinology 102:1909–1914[Abstract]
  24. Veldhuis JD, Johnson ML 1986 Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol 250:E486–E493
  25. Barb CR, Yan X, Azain MJ, Kraeling RR, Rampacek GB, Ramsay TG 1998 Recombinant porcine leptin reduces feed intake and stimulates growth hormone secretion in swine. Dom Anim Endocrinol 15:77–86[CrossRef][Medline]
  26. Sivitz WI, Walsh SA, Morgan DA, Thomas MJ, Haynes WG 1997 Effects of leptin on insulin sensitivity in normal rats. Endocrinology 138:3395–3401[Abstract/Free Full Text]
  27. Chen G, Koyama K, Yuan X, Lee Y, Zhou Y-T, O’Doherty R, Newgard CB, Unger RH 1996 Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy. Proc Natl Acad Sci USA 93:14795–14799[Abstract/Free Full Text]
  28. Emilsson V, Liu Y-L, Cawthorne MA, Morton NM, Davenport M 1997 Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 46:313–316[Abstract]
  29. Tannenbaum GS 1994 Multiple levels of cross-talk between somatostatin (SRIF) and growth hormone (GH)-releasing factor in genesis of pulsatile GH secretion. Clin Pediatr Endocrinol [Suppl 5] 3:97–110
  30. Quintela M, Señaris R, Heiman ML, Casanueva FF, Dieguez C 1997 Leptin inhibits in vitro hypothalamic somatostatin secretion and somatostatin mRNA levels. Endocrinology 138:5641–5644[Abstract/Free Full Text]
  31. Bruno JF, Olchovsky D, White JD, Leidy JW, Song J, Berelowitz M 1990 Influence of food deprivation in the rat on hypothalamic expression of growth hormone-releasing factor and somatostatin. Endocrinology 127:2111–2116[Abstract]
  32. Tannenbaum GS, Epelbaum J, Videau C, Dubuis J-M 1996 Sex-related alterations in hypothalamic growth hormone-releasing hormone mRNA- but not somatostatin mRNA-expressing cells in genetically obese Zucker rats. Neuroendocrinology 64:186–193,[Medline]
  33. Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, Hale J, Hoffmann J, Hsiung HM, Kriauciunas A, MacKellar W, Rosteck Jr PR, Schoner B, Smith D, Tinsley FC, Zhang X-Y, Heiman M 1995 The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 377:530–532[CrossRef][Medline]
  34. Rettori V, Milenkonic L Aguila MC, McCann SM 1990 Physiologically significant effect of neuropeptide Y to suppress growth hormone release by stimulating somatostatin discharge. Endocrinology 126:2296–2301[Abstract]



This article has been cited by other articles:


Home page
 J DAIRY SCIHome page
P. A. Accorsi, A. Munno, M. Gamberoni, R. Viggiani, M. De Ambrogi, C. Tamanini, and E. Seren
Role of Leptin on Growth Hormone and Prolactin Secretion by Bovine Pituitary Explants
J Dairy Sci, April 1, 2007; 90(4): 1683 - 1691.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
B. Bodosi, J. Gardi, I. Hajdu, E. Szentirmai, F. Obal Jr., and J. M. Krueger
Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1071 - R1079.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. A. Everson and W. R. Crowley
Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats
Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E1060 - E1070.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
L. L. Anderson, S. Jeftinija, and C. G. Scanes
Growth Hormone Secretion: Molecular and Cellular Mechanisms and In Vivo Approaches
Experimental Biology and Medicine, April 1, 2004; 229(4): 291 - 302.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
I. A. McDuffie, N. Akhter, and G. V. Childs
Regulation of Leptin mRNA and Protein Expression in Pituitary Somatotropes
J. Histochem. Cytochem., February 1, 2004; 52(2): 263 - 273.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
V. D. Dixit, M. Mielenz, D. D. Taub, and N. Parvizi
Leptin Induces Growth Hormone Secretion from Peripheral Blood Mononuclear Cells via a Protein Kinase C- and Nitric Oxide-Dependent Mechanism
Endocrinology, December 1, 2003; 144(12): 5595 - 5603.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
D. A. Zieba, M. Amstalden, M. N. Maciel, D. H. Keisler, N. Raver, A. Gertler, and G. L. Williams
Divergent Effects of Leptin on Luteinizing Hormone and Insulin Secretion Are Dose Dependent
Experimental Biology and Medicine, March 1, 2003; 228(3): 325 - 330.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. K. Hewson, L. Y.C. Tung, D. W. Connell, L. Tookman, and S. L. Dickson
The Rat Arcuate Nucleus Integrates Peripheral Signals Provided by Leptin, Insulin, and a Ghrelin Mimetic
Diabetes, December 1, 2002; 51(12): 3412 - 3419.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. L. Barker-Gibb, A. Sahu, C. R. Pohl, and T. M. Plant
Elevating Circulating Leptin in Prepubertal Male Rhesus Monkeys (Macaca mulatta) Does Not Elicit Precocious Gonadotropin-Releasing Hormone Release, Assessed Indirectly
J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4976 - 4983.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Watanobe and S. Habu
Leptin Regulates Growth Hormone-Releasing Factor, Somatostatin, and alpha -Melanocyte-Stimulating Hormone But Not Neuropeptide Y Release in Rat Hypothalamus In Vivo: Relation with Growth Hormone Secretion
J. Neurosci., July 15, 2002; 22(14): 6265 - 6271.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. S. Randeva, R. D. Murray, K. C. Lewandowski, C. J. O'Callaghan, R. Horn, P. O'Hare, G. Brabant, E. W. Hillhouse, and S. M. Shalet
Differential Effects of GH Replacement on the Components of the Leptin System in GH-Deficient Individuals
J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 798 - 804.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S.-G. Roh, G.-Y. Nie, K. Loneragan, A. Gertler, and C. Chen
Direct Modification of Somatotrope Function by Long-Term Leptin Treatment of Primary Cultured Ovine Pituitary Cells
Endocrinology, December 1, 2001; 142(12): 5167 - 5171.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. M. Ahmad, R. Guzder, A. M. Wallace, J. Thomas, W. D. Fraser, and J. P. Vora
Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement
J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3499 - 3506.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
D. Le Roith, C. Bondy, S. Yakar, J.-L. Liu, and A. Butler
The Somatomedin Hypothesis: 2001
Endocr. Rev., February 1, 2001; 22(1): 53 - 74.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
S. Nagatani, Y. Zeng, D. H. Keisler, D. L. Foster, and C. A. Jaffe
Leptin Regulates Pulsatile Luteinizing Hormone and Growth Hormone Secretion in the Sheep
Endocrinology, November 1, 2000; 141(11): 3965 - 3975.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. C. Henson and V. D. Castracane
Leptin in Pregnancy
Biol Reprod, November 1, 2000; 63(5): 1219 - 1228.
[Abstract] [Full Text]

Home page
 J. Histochem. Cytochem.Home page
S. Vidal, S. M. Cohen, E. Horvath, K. Kovacs, B. W. Scheithauer, B. G. Burguera, and R. V. Lloyd
Subcellular Localization of Leptin in Non-tumorous and Adenomatous Human Pituitaries: An Immuno-ultrastructural Study
J. Histochem. Cytochem., August 1, 2000; 48(8): 1147 - 1152.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. Maccario, G. Aimaretti, G. Corneli, C. Gauna, S. Grottoli, M. Bidlingmaier, C. J. Strasburger, C. Dieguez, F. F. Casanueva, and E. Ghigo
Short-term fasting abolishes the sex-related difference in GH and leptin secretion in humans
Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E411 - E416.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. A. Henry, A. J. Tilbrook, F. R. Dunshea, A. Rao, D. Blache, G. B. Martin, and I. J. Clarke
Long-Term Alterations in Adiposity Affect the Expression of Melanin-Concentrating Hormone and Enkephalin But Not Proopiomelanocortin in the Hypothalamus of Ovariectomized Ewes
Endocrinology, April 1, 2000; 141(4): 1506 - 1514.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. J. Suter, C. R. Pohl, and M. E. Wilson
Circulating Concentrations of Nocturnal Leptin, Growth Hormone, and Insulin-Like Growth Factor-I Increase before the Onset of Puberty in Agonadal Male Monkeys: Potential Signals for the Initiation of Puberty
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 808 - 814.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
L. Jin, S. Zhang, B. G. Burguera, M. E. Couce, R. Y. Osamura, E. Kulig, and R. V. Lloyd
Leptin and Leptin Receptor Expression in Rat and Mouse Pituitary Cells
Endocrinology, January 1, 2000; 141(1): 333 - 339.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Jin, B. G. Burguera, M. E. Couce, B. W. Scheithauer, J. Lamsan, N. L. Eberhardt, E. Kulig, and R. V. Lloyd
Leptin and Leptin Receptor Expression in Normal and Neoplastic Human Pituitary: Evidence of a Regulatory Role for Leptin on Pituitary Cell Proliferation
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2903 - 2911.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tannenbaum, G. S.
Right arrow Articles by Lapointe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tannenbaum, G. S.
Right arrow Articles by Lapointe, M.
Right arrowPubmed/NCBI databases
*Substance via MeSH

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals