G. R. Lakho  ( Departments of Physiology. Jinnah Medical College, Karachi. )
M. A. Qureshi  ( Department of Physiology, University of Karachi, Karachi. )

Since the identification and sequencing of ob-gene and its product leptin (146 amino acids chain; 16 KD protein) secreted from adipocytes¹, its role in body weight regulation and energy expenditure was extensively studied in rodents and humans^2-7. It is hypothesized that leptin plays a central role in energy homeostasis and human obesity^7-10. It has been postulated as a feedback regulator of adiposity leading to appetite suppression and catabolic effects^11-13. Leptin is known to act through interaction with receptors in the hypothalamus to induce a complex response involving fat mass regulation, and energy homeostasis^13-16.
Clinical aspects of leptin and its involvement in the pathophysiology of various disorders have also been discussed which emphasize its dual regulatory role in human physiology^16,18. Its relation with other peripheral and neural mechanisms involved in variety of physiological processes other than body weight regulation are being considered and are affected by its multifunctional diversity e.g. hematopoiesis. cardiovascular, immunity, proinflammatory responses and reproduction, including puberty and pregnancy^19-26. Leptin concentration and / or expression with certain metabolic indices and endogenous hormones e.g. GH, insulin, ACTI-I, CRH, CART, sex hormone, thyroid hormones and with certain disease conditions associated with obesity e.g. Prader-Willi Syndrome. D.M, obese diabetics, Cushing’s Syndrome, aging and in women with anorexia have been reported^27-39.
Evidence is accumulating that leptin has pleiotropic activities, exerting effect not only on appetite and metabolic rate but also on reproductive events^{8,10,25,40-46}. Thus, a putative role for leptin in human and rodent pregnancy and reproduction and importantly, in sexual maturation has been suggested^43,44,47,48. Body weight and adipocyte appear to play a critical role in the timing of puberty and increasing adiposity is associated with rise of leptin. Further, experimental evidence suggests that leptin is the signal that informs the brain about sufficiency of energy stores to support the high energy demands of reproduction and may be a major determinant of the timing of puberty⁴⁰. Leptin deficiency in ob/ob mouse is associated with hypogonadism and administration of recombinant leptin restores fertility^23,41,49. Leptin administration accelerated puberty in normal mice^23,40,50 and prevented the delay in ovulation induced by starvation in female mice⁵¹. It was demonstrated that normal pubertal mice after leptin administration had earlier maturation of reproductive tract and earlier reproduction, despite inhibition of growth rate²³. It is well known that low body fat disrupts the reproductive system, denionstrated by fall in testosterone levels associated with increased LH secretion in men and the changes have been accounted by the drop in leptin production²⁵ which suggests leptin action on hypothalamic-pituitary axis^51,52 The observation of increased ovarian steroid synthesis in vitro as well as increased primary and Graffian follicle numbers provided further evidence for trophic action of leptin which stimulates GnRH^41,53,54. In vivo, administration of estrogen increases circulating leptin in rodents and humans⁵⁵. Leptin is shown to interact directly or indirectly with both the adrenal and gonadal axes and its levels are higher in women than in men^56,57. Leptin inhibits CRH and hence ACTH and potentiates activity of GnRH neurons stimulating adrenal and gonadal functions, respectively^10,58,59. Synthesis of leptin from human pre-ovulatory follicles and relationship of leptin with gonadal hormones have also been reported^43,60. it was also found that that there is a slight decrease of leptin levels in postmenopausal (hypoestrogenem ic) compared to premenopausal women^55,61. Rise in leptin levels at the onset of puberty⁶² and fall in postmenopausal women and its relationship with gonadotroph ins suggests an association of leptin’s changing concentrat ion with reproductive events. Oopherectomy of adult rats cause a significant decline in circulating leptin concentration that is reversed by estradiol supplementation⁶⁵. Estradiol increases in vitro leptin production in omental adipose tissue of women but not men⁶³. Circulating concentration of estradiol and testosterone have been reported to be significantly correlated with plasma leptin concentration in adult women⁶⁴, but not in female children or adolescents⁶⁵. Leptin concentration was negatively correlated with circulating testosterone in men. Circulating plasma leptin concentrations normalized to body weight mass index are significantly increased in hypogonadal as compared to eugonadal men. Leptin concentration is lowered in hypogonadal men after administration of testosteronebô. Circulating leptin’s sexual dimorphism has been reported⁶¹. Thus, leptin increase may be involved in either control or onset of puberty, known to be linked to the fat acquisition^40,67-69. All these direct or indirect evidences therefore support the hypothesis that leptin may be the signal responsible for triggering the onset of pubescence in human beings⁷⁰. The data suggests that leptin. acts as a signal to trigger puberty, thus supporting the hyp⁹ Thesis that fat accumulation enhances maturation of the reproductive tract. Thus. leptin may be one of the hormonal signals to the brain when the body is ready for maturation.
The relationship between leptin levels, steroid hormones and gonadotrophin concentrations during the menstrual cycle has been studied^71-73. Plasma leptin level was found to increase during the late follicular and luteal phases of the menstrual cycle. Changes in circulating leptin levels were associated with menstrual phases and peak levels during luteal phases correlated with high progesterone levels. The cause of this relationship remains unknown. It may be that augmented adipocyte production of leptin in response to increased caloric intake occurs. Alternatively, there may be release of hypothalamic neuropeptide Y or release of leptin from mature ovarian follicles. A large body of evidence now supports the existence of a negative feedback system regulating food intake, leptin secretion and hypothalamic neuropeptide NPY expression^52,74,75. The role of leptin in regulation of menstrual cycle and in preparing the body for the metabolic demands of pregnancy has been suggested⁷². Relationship between leptin and human reproduction is well documented. The possible role of leptin in various conditions like puberty, polycystic ovary syndrome and pregnancy as well as in ovarian functions and relationship with gonadal steroids has been reviewed^54,60,70,71. However, physiological significance of many of these processes remains unclear.
Pregnancy is a physiological state associated with the alterations in food intake, energy expenditure, body weight and metabolism. The mechanisms by which maternal weight is regulated during pregnancy, particularly during the third trimester are poorly understood. One of the well known factors that increase the body weight during pregnancy is an increase in body fat tissue mass, providing the researchers with the assumption that leptin level increases during pregnancy. Scarce data exists with respect to leptin levels and its potential role during human pregnancy at term, data regarding relationship between maternal leptin and neonatal leptin levels is controversial in many aspects^76,77. Although increased levels of leptin during pregnancy have been documented^71,73,76,81, the functional significance, the sources and stimuli of leptin in maternal physiology are still not clear. However, the changes in circulating leptin parallel the process of fat accumulation and mobilization. Leptin has been found to correlate positively with weight, BMI, body fat mass and percentage of fat mass^3,5,76,79. On the other hand, no correlation was found between maternal serum leptin levels and BMI⁷⁷. Thus, at term, it remains controversial.
However, study in Pakistani subjects showed positive correlation between serum leptin levels and BMI at delivery⁸¹. In another study on humans, leptin concentration was increased progressively during the first two trimesters peaking at 28th week. The levels also correlated significantly with maternal weight and BMI²⁶. Significant increase in leptin between the first two trimesters of pregnancy but not between second and third trimesters were also demonstrated⁷³, suggesting that several hormones of pregnancy may contribute to increased leptin secretion. In pregnancy, appetite is increased and low leptin levels would be expected. In fact, the opposite is true and leptin levels in pregnancy are high. Leptin increase significantly during early pregnancy before any change in body fat and resting metabolic rate suggesting that pregnancy might represent a leptin resistance state⁸², while evaluating longitudinal changes in maternal leptin concentration, body composition and metabolic rate during early and late pregnancy in comparison to the pre-pregnancy state. In another study hyperleptinemia in pregnancy was attributable to binding of leptin to a form of leptin receptor secreted by the placenta⁸³. Rise in leptin during pregnancy was due to expression of a binding protein, which was found to have sequence identity to the extracellular domain of the leptin receptors. The placenta was found to produce large amount of the ob-Re isoform of leptin receptors mRNA, while encodes a soluble binding protein. Binding of the leptin by a secreted form of the leptin receptors (from placenta) may be the cause of extreme hyperleptineamia of late pregnancy⁸³. Placental basis for leptin production has also been documented through expression studies⁸⁴. The placenta as a major source of leptin in fetal circulation is also supported by higher leptin levels in umbilical cord veins than in umbilical cord arteries and marked decrease during the neonatal period⁸⁵. Increased concentration of leptin during pregnancy and in newborn infants supports contribution of placenta to the high levels of leptin found in umbilical cord suggesting a role of leptin in intrauterine growth and development⁸⁰.
Although a relationship between leptin and the reproductive, processes clearly exists, the precise regulatory role of leptin in the menstrual cycle and pregnancy is not understood. Studies have suggested mechanisms by which
leptin may effect hypothalamic-pituitary-ovarian axis, this includes hypothalamic neuropeptide Y expression and/or presence of receptors in ovaries, which awaits confirmation.

1.Zhang, Y., Proenca, R., Maffei, M., et al. Positional cloning of the mouse gene and its human homologue. Nature., 1994; 372 425-32.
2.Ualaas, J. L.. Gajiwala,K S.. rnaffei. M., et at Weight reducing effect of plasma protein encoded by the obese gene. Science., 1995: 269: 543-45.
3.Maffei, M., l-lalaas. J., Ravussm, E., et al. Lcptin levels in human and rodent measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Med., 1995: 11: 1155-61.
4.Pellcvmounter, MA., Cullen, M. J., Baker, MB., et al. Effect of the ob gene product on body weight regulation in ob/ob mice. Science., 1995; 269 540-43.
5.Considine, K. V., Sinha, M. K., Heiman, M. L.. et al. Serum immunoreactive­leptin concentration in normal-weight and obese humans N. Engl. J. Med.,1996:334 292-95.
6.Sinha, M.K.. Opentanova, I., Ohannesian, J P., et al. Evidence of free and bound leptin in human circulation. .J. Clin.Invest.. 1996: 98: 1277-82.
7.Montague, CT.. Sadal Farooqi. I., Whitehead, J. P., cm al. Congenital leptin deficiency is associated with severe early onset obesity in humans. Nature.,1997: 387: 903-9.
8.Halaas, 3. L., Boozer, C., Blair-West, 3., et al. Physiological response to long term peripheral and central lcptin infusion in lean obese mice. Proc. Nat. Acad. Scj,, USA l997 : 94:8878-83.
9.Jequir, E. and Tappy. L. Regulation of body weight in humans, Physiol. Rev,,1999; 79: 451-480.
10.Montzoros, C. S. The role of leptin in human disease: a review of current evidence. Ann. Intern. Med., 1999; 130:671-80.
11.Caro, J. F., Sinha, M. K., Kolaczynski, J. W., et al Leptin: The tale of an obesity gene. Diabetes., 1996; 45: 1445-62.
12.Auwerx, J,, Staels, B. Leptin. Lancet., 1998; 351(9104): 737-42.
13.Houseknecht, K.L., Baile, CA., Matteri, R.L., em al. The biology of leptin: a review. J.Animal. Sci.., 1998; 76: 1405-20.
14.Tartaglia, L. A., Demski, M., Weng, X., et al. Identification and expression cloning ofaleptin receptor. Cell,, 1995; 83:1263-71.
15.Roberts, S. B., and Greenberg. A. .S The new obesity gene. Nut. Rev.,1996; 54: 41-49.
16.Sinha, M. K.. Caro. J. F.. Clinical aspect of leptin. Vitam-Honn., 1998; 54:1-30.
17.Fruhbeck. G., Jebb, S. A., Prentice. A. M. Leptin’ Physiology and pathophysiology. Clin. Physiop.. 1998; 18(5): 399-419.
18.Montzaros, C. S. and Moschos, S. J. Leptin: in search of roles in human physiology and pathology. Clin Endocrinol., 1998; 49: 55 1-567.
19.Wilson, CA., Bekele, G., Nicolson, M., et al. Relationship between white blood cell count to body fat: role of leptin. Br. J. H aematol., 1997; 99: 447-51.
20.Couillard, C., Mauriege, P., Prud’homme, D., et al. Plasma leptin concentrations: gender differences and association with metabolic risk factors for cardiovascular diseases. Diabetologia, 1997: 40 It 78-84.
21.Lord, G. M., Matarese. G., Howard, . K.. et al Leptin modulates the T cell immunity response and reverses starvation induced immunosuppression. Nature.,1998: 394: 897-98.
22.Loffreda, S., Yang. S. Q., Lin, H. Z., et al. Leptin regulates proinflammatory immune responses. FASEB 3., 1998; 12: 57-65.
23.Chehab, F., Mounzih, K., Lu, R. et al. Early onset of reproductive function in normal mice treated with leptin. Science., 1996; 2275: 88-90.
24.Cunningham, M. J., Clifton, D. K., Steiner, R. A. Leptin’s action on reproductive axis: perspectives and mechanisms. Biol. Reprod., 1999; 60:216-22.
25.Kiess, W., Blum, W. F., Aubert, M. L. Leptin, puberty and reproductive
function: lession from animal and mechanisms. Biol Reprod., 1999;60: 216-22.
26.Tamas, Paa., Sulyok, E., Szabo, I., et al. Changes of maternal serum levels during pregnancy. gynecol. Obstet Invest., 1998:46: 169-71.
27.considine, R. V., Weight regulation, leptin and growth honnone. Horm Res., 1997;48 Suppl 5: 116-21.
28,Hanley, A. J., Harris, S. B., Gao, X. J., et al. Serum immunoreactive tepun concentrations in a Canadian aboriginal population with high rates of NIDDM. Diabetes Care.,1997; 20: 1408-15.
29.Wand, G. S., Schumann, H. Relationship between plasma adrenocorticotropin, hypothalamic opioid tone and plasma leptin. J. Clin. Endocrinol. Metab., 1998;83: 2183-42.
30.Uehara,Y., Shimizu, H., Ohtani, K., et al. Hypothalamic-corticotropic­releasing hormone isa mediator of the anorexigenic effect of leptin. Diabetes., 1998; 47; 890-3.
31.Widmaier E. P.. Long, J., Cadigan, B., et al. Leptin corticotropin-relasing hormone (CRH), and neuropeptide Y (NPY) in free ranging pregnant bats. Endocrine.,1997; 7(2): 145-50.
32.Knstensen, P., Judge, M. E., Thim. L., et al. Hypothalamic CART is a new anorectic peplide regulated by leptin. Nature., 1998; 393: 72-6.
33.Poalisso, G., Rizzo, M., Mone, C., et at. Plasma sex hormones are significantly associated with plasma leptin concentration in healthy subjects. Clin. Endocrin. Oxf.. 1998; 48: 291-97.
34.Yoshida, T., Momotani, N., Hayashi, M., et al. Serum teptin concentrations in patients with thyroid disorders. Clin, Endocrinol. Oxf., 1998; 48: 299-302.
35.Kiess, W., Anil, M., Blum, W. F., et al. Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index. Eur. J. Endocrinol..1998: 138: 501-9.
36.Tasaka, V., Yanagisawa, K., twamoto, V. Human plasma leptin in obese subjects and diabetics. Endocnnol J.,1997, 44: 67 1-6.
37.Widjaja, A., Schurmeyer, T. H., Von zor Muhien, A., et al. Detenninants of serum leptin levels in Cushings syndrome. J. Clin. Endocrinol. Metab., 1998; 83: 600-3.
38.Moller, N., O’Brien, P., Nair, K. S., Disruption of relationship between fat content and leptin levels with aging in humans. 3. Clin. Endocrinol. Metabol., 1998,83: 931-4.
39.Baranowska, B., Wasilewska-Dziubinska, E., Randzikowska, M., et at. Neuropeptide Y, galanin, and leptin release in obese women and in women with anorexia nervosa. Metabolism., 1997; 46: 1384-9.
40.Ahima, R. S., Dushay, J., Flier, S. N., et at. Leptin accelerates the onset of puberty in normal female nice. J.Clin. Invest., 1997; 99: 39 1-95.
41.Barassh, I. A., Cheung, C. C. and Wiegle, D. S. Leptin is a metabolic signal to the reproductive system. Endocrinology., 1996; 137: 3144-47.
42.Tomimatsu, 1., Yamaguchi, M., Murakami, T., et at. Increase of mouse leptin production by adipose tissue after mid pregnancy: gestational profile of serum leptin concentration. Biochem. Biophys. Res. Commun., 1997; 240: 213-5.
43.Rosenbaum, M. and I.eibel, R. L. Role of gonadal stcnods in the sexual dimorphisms in body composition and circulating concentration of lepiin. J. Clin. Endocrinol. Metab., 1999; 84: 1784-1789.
44.Cunningham, M. 3., Clifton, D. K. and Steiner, R. A. Leptin’s action on the reproductive axis: perspectives and mechanism. Blot .Reprod., 1999; 60: 216­ 22.
45.Foster, D. L and Nagatani, S. Physiological perspective on leptin as a regulator of reproduction: role in timing puberty. Biol. Reprod., 1999; 60:
205-15.
46.Messinis, I. E. and Milingos, S. D. Leptin in human reproduction. Hum Reprod Update., 1999; 5:52-63.
47.Steiner, R. A. (Editorial). Ltords and ladies teapin’ on teptin. Endocrinology., 1996; 137’ 4533-34.
48.Vogel, G. Leptin: A trigger for puberty?. Science., 1996; 274 1466-49. Chehab, F., Lim, M. and Lu, R. Correction of sterility defect in homozygous obese female mice by treatment with recombinant teptin. Nature Gen., 1996; 12 318-320.
50.Cheung, C. C., Thornton, 3. E.. Kuijper, J L et al. Leptin is a metabolic gate for the onset of puberty in female rat. Endocrinology, 1997; 138: 855-858-3147.
51.Ahima, R. S., Parabakra, D., Montzoros, C., et at. Rote of teptin in the neuroendocrine response to fasting. Nature., 1996; 382: 250-52.
52.Cainpfield, L. A., Smith,F. 3., Guisez, V., et at. Recombinant mouse ob protein . Evidence for a peripheral signal linking adiposity and central neural network. Science., 1995; 269: 546-49.
53.Vu, W. H., Kimura, M., Walczewska, A., et at. Role of leptin in hypothalamic pituitary function. Proc. Nate, Acad. Sci. USA., 1997; 94: 1023-28.
54.Zachow, R W and Magoffin, D. A. L)irect intraovarian effects of leptin: impairment of the synergistic action of insulin like growth factor-l on follicle stimulating hormone-dependant estradiol 17 production by rat ovarian granulosa cells. Endocrinology., 1997; 138:847-850.
55.Shimizu, H, Shimomura, V., Nakanishi, V., et al. Estrogen increase in vivo leptin production in rats and human subjects. J. Endocrinol., 1997; 154: 285-92.
56.Licinio, 3., Mantzoros, C.. Negrao, A. B., ci at. Human leptin levels are pulsatile and inversely related to pituitary-adrenal functions. Nat. Med.. 1997;3: 575-9.
57.Saad, M. F., Damani, S., Gingerich, R. L, et al. Sexual dimorphism in plasma leptin concentration. . 3. Clin. Endocrinol. Metab., 1997; 82: 579-84.
58.Bronstein, S. R., Uhlmann, K., Haidan, A. et at. Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland. leptin inhibits cortisot release directly. Diabetes., 1997; 46: 1235-42.
59.Heiman, M. L., Ahima, R. S., Craft, L. S.. ci al. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology., 1997; 138: 3859-63.
60.Cioffi, 3. A., Van Blerkom J., Antczak, M,, et al. The expression of leptin and its receptor in pre-ovulatory human follicles. Mol. Hum. Reprod., 1997; 3: 467-72.
61.Rosenbaum, M., Nicolson M., Hirsch, J., ci at. Effect of gender, body composition, and menopause on plasma concentration of lepiin J. Clin. Endocrinol. Metab, 1996; 81: 3424-27.
62.Hassink, S. G., Sheslow, D. V., Detancey, E., et at. Serum leptin in children with obesity relationship to gender and development. Pediatrics., 1996; 98: 201-3.
63.Casebielli, X., Pineiro, V., Peino, R., ci at. Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro: Dexamethasone and estradiol stimulated teptin release in women, but not in men. J. Clin. Endocrinol. Metab., 1998; 83: 2 149-2155.
64.Perry, H., Morley, J., Horowit, M., et al. Body compoition and age in african-american and caucasian women: relationship to plasma leptin levels. Metabotis.. 1997; 46: 1399-1405.
65.Ambrosius, W., Compton, J., Bowsher, R., et at. Relationship of race, age and sex honnone differences to serum leptin concentration in children and adolescents. Honn. Res., 1998; 49: 240-46.
66.Jockenhovel, F., Blum, W., Vogol, E., et at. Testosterone substitution normalizes elevated serum leptin levels in hypogonadal man. . J. Clin. Endocrinol. Metab., 1997; 82: 25 10-13.
67.Garcia-Mayor, R. V., Andrade, M. A., Rios, M., et at. Serum leptin levels in nonnal children: relationship to age, gender, body mass index, pituitary­gonadal honnones, and pubertal stage. 3. Clin. Endocrinol. Metab., 1997., 82: 2849-55.
68.Matkovic, V., Llich, J. Z., Bademhop N   et at. Gain in body fat is inversely related to the noctumal rise in serum leptin levels in young females.. J. Clin. Endocrinol. Metab.. 1997., 82: 1368-72.
69.Chrousos, G. P., Torpy, D. 3. and Gold. P. W. Hypothalamic-Pituitary-Adrenal Axis and the female reroductive system: Clinical implications. Ann. Int Med., 1998., 129:229-40.
70.Mantzoros, CS., Flier, S. and Rogol. A. D. A longitudinal assessment of hormonal and physical alteration during normal puberty in boys. Rising leptin levels may signal the onset of puberty. J. Clin. Endocrinol. Metab.. 1997; 82: 1060-1070.
71.Hardie, L., Trayuhurn, P., Abramovich. D., et at. Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin. Endocrinol., 1997; 47: 101-6.
72.Riad-Gabriel, M. G., Jinagouda, S. D., Sharma, A., ci at Changes in plasma leptin during the menstrual cycle. Eur. 3. Endocrinol., 1998; 139:528-31.
73.Sivan, E., Whittaker, PG., Sinha. D., et at. Leptin in human pregnancy: the relationship with gesiational hormones. Am. J. Obstet. Gynecol., 1998; 179: 1128-32.
74.Schwartz, M. W. and Seetey, R. J. Neuroendocrine responses to starvation and weight loss. N. EngI. J. Med.. 1997; 334: 324-5.
75.Schwartz, M. W. Baskin. D. G., Kaiyala, K. J., et al. Model for the regulation of energy balance and adiposity by the central nervous system. Am. 3. Clin. Nutr., 1999; 69: 584-96.
76.Butte, N.F., Hopkinson, J. M., and Nicolson, M A. Leptin in human reproduction: serum leptin levels in pregnant and lactating women. J. Clin. Endocrinol. Metab., 1997; 82: 585-89.
77.Schubnng, C., Kiess, W., Englaro. P., et al. Levels of leptin in maternal senim, amniotic fluid, and arterial and venous cord blood: Relation to neonatal and placental weight. J. Clin Endocrinol. Metab., 1997; 82: 1480-83
78.Masuzaki, H Ogawa. Y., Sagawa, N., et al. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med., 1997;3:1029-33,
79.Sattar, N., Greer, I. A., Pirwani, I., et al. Leptin levels in pregnancy: marker for fat accumulation and rnobiliztaion? Acta. Obstet. Gynecol. Scand.. 1998; 77:278-83.
80.Helland, I. B., Reseland, J. E., Saugstad, 0. 0., et al. Leptin levels in pregnant women and new born infants: gender differences and reduction during the neonatal period. Pediatrics.. 1998; 101 :E 12.
81.Lakho, G. R. and Qureshi, M. A. 7th Biennial Conference, Pakistan Physiological Society Karachi, 2000., p. 27.
82.Highrnan, 1. 3., Friedman, J, E., Huston, L. P., et al. Longitudinal changes in matemal serum leptin concentration, body composition, and resting metabolic rate in pregnancy. Am. 3. Obstet. Gynecol., 1998; 178: 1010-5.
83.Gavrilova, 0., Barr, V., Marcus-Samuels, B.. et al. Uyperleptinemia of pregnancy associated with the appearance of a circulating form of leptin receptor. J. Biol. Chem., 1997: 272: 30546-51.
84.Bi, S., Gavrilova, 0., Gong, 0W., et al. Identification of placental enhancer/for the human leptin gene. 3. Biol. Chem., 1997: 272: 30583-8.
85.Yura, S., Sagawa, N., Misc, H., et al. A positive umbilical venous-arterial difference of leptin level and its rapid decline after birth. Am. J. Obstet. Gynecol., 1998; 178: 926-30.