The International Journal of Romanian Society of Endocrinology / Registered in 1938

in Web of Science Master Journal List

Acta Endocrinologica(Bucharest) is live in PubMed Central

Journal Impact Factor - click here.

April - June 2005, Volume 1, Issue 2
General Endocrinology

Poiana C, Stefanescu AM, Caragheorgheopol A, Badiu C, Galoiu S, Coculescu M

Blood brain barrier by-pass produced by pituitary adenomas for pituitary peptides does not involve leptin

Acta Endo (Buc) 2005, 1 (2): 157-166
doi: 10.4183/aeb.2005.157

Introduction: The impaired transport of leptin into the brain through a decreased permeability of the blood-brain barrier (BBB) for leptin in obesity represents one of the important mechanisms involved in leptin resistance which is characteristic in human obesity. Some pituitary tumors can increase the blood-cerebrospinal fluid barrier (BCB) permeability for peptides. BCB is a part of BBB.\r\nObjectives: The aim of our study was to search if the by-pass of BCB for pituitary hormones produced by adenomas does influence the transport of leptin into the central nervous system in obese patients.\r\nMaterials and methods: We investigated 20 males with pituitary adenomas: group A (11 patients) had cerebrospinal fluid (CSF) to serum ratio more than one for prolactin (PRL) and in some patients for growth hormone (GH) and follicle stimulating hormone (FSH), suggesting an increased permeability of BCB and a control group C (9 patients), which had CSF/serum ratio less than one for GH, PRL or FSH, suggesting an intact BCB. Both A and C groups contain subgroups of patients with obesity (body mass index, BMI>30 kg/m2) and normal body weight (BMI<25 kg/m2). In these patients we measured the CSF to serum leptin ratio in order to clinically evaluate the leptin transport into the brain. Rapid fluoroimmunoassay method with europium was used. Leptin was assayed by ELISA method.\r\nResults: The patients of group A with pituitary adenomas show a higher level of pituitary peptides, PRL and in some cases GH, FSH in CSF as compared to serum (ratio CSF/serum over 1), both in obese and non-obese. By contrast, in the same patients, there is\r\na low level of CSF leptin as compared to serum leptin (ratio CSF/serum less than 1). In the subgroup of obese patients from group A we found even less ratio of CSF to serum leptin, than in non-obese. There is a well known higher leptin concentration in the plasma of obese patients with pituitary adenomas as compared to non-obese ones (26.4?3.8ng/ml vs 12.4?3.4ng/ml, p<0.05). In the control group C, both pituitary peptides (PRL, or GH, FSH) and leptin showed a ratio CSF/serum less than 1, in all patients.\r\nConclusions: These data show a decrease in hemato-encephalic barrier permeability for leptin in obese patients through a specific mechanism, not influenced by other peptides passing through injuries of BBB produced by pituitary adenomas. It is tempting to suggest that there is a specific by-pass of BCB for pituitary peptides, in some pituitary adenomas.

Keywords: leptin, blood brain barrier, cerebrospinal fluid, obesity, pituitary adenomas

Correspondence: Mihail Coculescu, Endocrinology Department, ?Carol Davila? University of Medicine and Pharmacy, 34-36 Bd. Aviatorilor, 011863, Bucharest, Romania, Tel/Fax; + 4021 3198718, e-mail;


1. Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 2000; 143(3):293-311. [CrossRef]
2. Rodrigues AM, Radominski RB, Suplicy HL, De Almeida SM, Niclewicz PA, Boguszewski CL. The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity. J Clin Endocrinol Metab 2002; 87(4):1621-1626. [CrossRef]
3. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84(3):491-495.
4. Tartaglia LA. The leptin receptor. J Biol Chem 1997; 272(10):6093-6096.
5. Fei H, Okano HJ, Li C, Lee GH, Zhao C, Darnell R et al. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc Natl Acad Sci U S A 1997; 94(13):7001-7005. [CrossRef]
6. Burguera B, Couce ME, Curran GL, Jensen MD, Lloyd RV, Cleary MP et al. Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats. Diabetes 2000; 49(7):1219-1223. [CrossRef]
7. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334(5):292-295. [CrossRef]
8. Poiana C, Cucu M, Stefanescu A, Stoian L. Are plasma leptin levels predictive for the bone mineral density in postmenopausal women? Bone 2005; 36(Suppl 2):S341-S342.
9. Coculescu M, Gheorghiu M, Galoiu S, Trifanescu R, Caragheorgheopol A, Hortopan D et al. Natural and therapeutically-induced evolution of serum and cerebrospinal fluid pituitary hormones in patients with pituitary adenomas. The XIth Symposium of Psychone
10. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348(9021):159-161. [CrossRef]
11. Wong ML, Licinio J, Yildiz BO, Mantzoros CS, Prolo P, Kling M et al. Simultaneous and continuous 24-hour plasma and cerebrospinal fluid leptin measurements: dissociation of concentrations in central and peripheral compartments. J Clin Endocrinol Metab 2 [CrossRef]
12. Saad MF, Riad-Gabriel MG, Khan A, Sharma A, Michael R, Jinagouda SD et al. Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrinol Metab 1998; 83(2):453-459. [CrossRef]
13. Kennedy A, Gettys TW, Watson P, Wallace P, Ganaway E, Pan Q et al. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab 1997; 82(4):12 [CrossRef]
14. Nam SY, Kratzsch J, Kim KW, Kim KR, Lim SK, Marcus C. Cerebrospinal fluid and plasma concentrations of leptin, NPY, and alpha-MSH in obese women and their relationship to negative energy balance. J Clin Endocrinol Metab 2001; 86(10):4849-4853. [CrossRef]
15. Zlokovic BV, Jovanovic S, Miao W, Samara S, Verma S, Farrell CL. Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal [CrossRef]
16. Wiesner G, Vaz M, Collier G, Seals D, Kaye D, Jennings G et al. Leptin is released from the human brain: influence of adiposity and gender. J Clin Endocrinol Metab 1999; 84(7):2270-2274. [CrossRef]
17. Vidal S, Cohen SM, Horvath E, Kovacs K, Scheithauer BW, Burguera BG et al. Subcellular localization of leptin in non-tumorous and adenomatous human pituitaries: an immuno-ultrastructural study. J Histochem Cytochem 2000; 48(8):1147-1152.
18. Coculescu M, Poiana C, Pop A, Oprescu M, Constantinovici A, Simionescu N. Altered specificity of the blood cerebrospinal fluid barrier for pituitary hormones in patients with tumoral hypothalamohypophyseal diseases as proved by releasing hormones stimul