Prolactin Inhibition in Lactating Rats Changes Leptin Transfer through the Milk

Abstract

Malnutrition during lactation reduces milk production and changes pup’s leptin serum levels. To test prolactin role in this nutritional state, we evaluated whether prolactin suppression during lactation changes serum leptin in dams, its transfer through the milk, and pup’s serum leptin. Lactating rats were treated with bromocryptine (1 mg/twice a day, sc) or saline three days before sacrifice (days 2 - 4 or days 19 - 21). Food intake and body weight were measured until sacrifice (4^th and 21^st day). Serum prolactin and leptin were determined by radioimmunoassay. Bromocryptine injected dams had lower serum prolactin and milk production as expected. The mothers presented lower food ingestion (day 21: - 25 %), lower body weight (day 4: - 12 %; day 21: - 10 %), higher serum leptin (day 4: + 68 %), lower milk leptin on the 4^th day (11 times) and higher (8 times) on the 21^st day. The offspring of bromocryptine-treated mothers presented lower body weight in both periods of lactation and lower serum leptin on the 4^th day (- 40 %) and higher on the 21^st day (+ 37 %) of lactation. We suggest that prolactin, through its effect on leptin secretion into the milk, may play an important role in signalizing maternal nutritional status to the pups.

Bromocryptine - Prolactin - Leptin - Lactation - Rat

References

• 1 Passos M CF, Ramos C F, Moura E G. Short and long term effects of malnutrition in rats during lactation on the body weight of offspring.  Nutr Res. 2000;  20 1603-1612
• 2 Passos M CF, Ramos C F, Dutra S CP, Moura E G. Long-term effects of malnutrion during lactation on the thyroid function of offspring.  Horm Metab Res. 2002;  34 40-43
• 3 Lucas A. Programming by early nutrition: an experimental approach.  J Nutrition. 1998;  128 401-406
• 4 Passos M CF, Ramos C F, Dutra S CP, Moura E G. Transfer of iodine through the milk in protein-restricted lactating rats.  J Nutr Biochem. 2001a;  12 300-303
• 5 Passos M CF, Ramos C F, Moura E G. Increase of T3 secreted through the milk in protein restricted lactating rats.  Nutr Res. 2001b;  21 917-924
• 6 Lisboa P C, Passos M CF, Dutra S CP, Santos R S, Bonomo I T, Cabanelas A P, Pazos-Moura C C, Moura E G. Increased 5’-iodothyronine deiodinase activity is a maternal adaptative mechanism in response to protein restriction during lactation.  J Endocrinol. 2003;  177 261-267
• 7 Teixeira C V, Passos M CF, Ramos C F, Dutra S CP, Moura E G. Leptin serum concentration, food intake and body weight in rats whose mothers were exposed to malnutrition during lactation.  J Nutr Biochem. 2002;  13 493-498
• 8 Cravo C O, Teixeira C V, Passos M C, Dutra S C, de Moura E G, Ramos C. Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats.  Horm Metab Res. 2002;  34 400-405
• 9 Teixeira C V, Ramos C D, Mouco T, Passos M C, De Moura E G. Leptin injection during lactation alters thyroid function in adult rats.  Horm Metab Res. 2003;  35 367-371
• 10 Ahren B O, Mansson S, Gingerich R L, Havel P J. Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting.  American Journal Physiology. 1997;  273 113-120
• 11 Trottier G, Koski K G, Brun T, Toufexis D J, Richard D, Walker C D. Increased fat intake during lactation modifies hypothalamic-pituitary-adrenal responsiveness in developing rat pups: a possible role for leptin.  Endocrinology. 1998;  139 3704-3711
• 12 Sauter E R, Garofalo C, Hewett J, Hewett J E, Morelli C, Surmacz E. Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced by body mass index (BMI) but not by the presence of breast cancer.  Horm Metab Res. 2004;  36 336-340
• 13 Casabiell X, Piñeiro V, Tomé M A, Peinó R, Diéguez C, Casanueva F F. Presence of leptin in colostrum and/or breast milk from lactating mothers: a potencial role in the regulation of neonatal food intake.  J Clin Endocr Metab. 1997;  82 4270-4273
• 14 Mukherjea R, Castonguay T W, Douglass L W, Moser-Veillon P. Elevated leptin concentrations in pregnancy and lactation: possible role as a modulator of substrate utilization.  Life Sciences. 1999;  65 1183-1193
• 15 Gonzalez L C, Pinilla L, Tena-Sempere M, Aguilar E. Leptin stimulates prolactin and luteinizing hormone secretion in fasted adult male rats.  Neuroendocrinol. 1998;  70 213-220
• 16 Yu W H, Kimura M, Walczewska A, Karanth S, McCann S M. Role of leptin in hypothalamic-pituitary function.  Proc Natl Acad Sci. 1997;  94 1023-1028
• 17 Hardie L J, Rayner D V, Holmes S, Trayhurn P. Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not zucker (fa/fa) rats as measured by ELISA.  Biochem Biophys Res Commun. 1996;  223 660-665
• 18 Mantzoros C S, Moschos S J. Leptin in search of role in human physiology and pathophysiology.  Clin Endocrinol. 1998;  49 551-567
• 19 Gualillo O, Lago F, García M, Menéndes C, Señarñs R, Casanueva F F, Diéguez C. Prolactin stimulates leptin secretion by rat white adipose tissue.  Endocrinol. 1999;  140 5149-5153
• 20 Brogan R S, Mitchell S E, Trayhurn P, Smith M S. Supression of leptin during lactation: contribution of the suckling stimulus versus milk production.  Endocrinol. 1999;  140 2621-2627
• 21 Flint D J, Vernon R G. Effects of food restriction on the responses of the mammary gland and adipose tissue to prolactin and growth hormone in the lactating rat.  J Endocrinol. 1998;  156 299-305
• 22 Sauvé D, Woodside B. The effect of central administration of prolactin on food intake in virgin female rats is dose-dependent, occurs in the absence of ovarian hormones and the latency to onset varies with feeding regimen.  Brain Res. 1996;  729 75-81
• 23 Pickavance L, Tadayyon M, Williams G, Vernon R G. Lactation Suppresses Diurnal Rhythm of Serum Leptin.   Biochem Biophys Res Commun. 1998;  248 196-199
• 24 Amico J A, Thomas A, Crowley R S, Burneister L A. Concentrations of leptin in the serum of pregnant, lactating, and cycling rats and of leptin messenger ribonucleic acid in rats placental tissue.  Life Sci. 1998;  63 (16) 1387-1395
• 25 Denis R G, Williams G, Vernon R G. Regulation of serum leptin and its role in the hyperphagia of lactation in the rat.  J Endocrinol. 2003;  176 193-203
• 26 Amenomori Y, Chen C L, Meites J. Serum prolactin levels in rats during different reproductive states.  Endocrinology. 1970;  86 506-510
• 27 Noel M B, Woodside B C. Effects of systemic and central prolactin injections of food intake, weight gain, and estrous cyclicity in female rats.  Physiol Behav. 1993;  54 151-154
• 28 Heil S H. Sex-specific effects of prolactin on food by rats.  Horm Behav. 1999;  35 47-54
• 29 Moore B J, Gerardo-Gettens T, Horwitz B A, Stern J S. Hyperprolactnemia stimulates food intake in the female rat.  Brain Res Bull. 1986;  17 563-569
• 30 Byatt J C, Staten N R, Salsgiver W J, Kostelc J G, Collier R J. Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone.  Am J Physiol. 1993;  264 E986-E992
• 31 Fleming A S. Control of food intake in the lactating rat: role of suckling and hormones.  Physiol Behav. 1976;  17 841-848
• 32 Pine A P, Jessop N S, Allan G F, Oldham J D. Maternal protein reserves and their influence on lactional performance in rats: tissue protein synthesis and turnover associated with mobilization of maternal protein.  Br J Nutr. 1994 a;  72 831-844
• 33 Cambraia R PB, Vannucchi H, De-Oliveira L M. Food intake and weight of lactating rats maintained on different protein-calorie diets, and pup growth.  Braz J Med Biol Res. 1997;  30 985-988
• 34 Rasmussen K M. Effects of under and overnutrition on lactation in laboratory rats.  J Nutr. 1998;  128 390S-393S
• 35 Strode M A, Dewey K G, Lönnerdal B. Effects of short-term caloric restriction on lactational performance of well-nourished women.  Acta Paediatr. 1986;  75 222-229
• 36 Ben-Jonathan N, Hnasko R. Dopamine as a prolactin (PRL) inhibitor.  Endocr Rev. 2001;  22 724-763
• 37 Bayne K. Revised Guide for the Care and Use of Laboratory Animals available.  American Physiology Society. 1996;  39 208-211
• 38 Fishbeck K L, Rasmussen K M. Effect of repeated cycles on maternal nutritional status, lactational performance and litter growth in ad libitum-fed and chronically food-restricted rats.  Journal of Nutrition. 1987;  117 1967-1975
• 39 Hassink S G, deLancey E, Sheslow D V. Placental leptin an important new growth factor in intrauterine and neonatal development?.  Pediatrics. 1997;  100 e1-e6
• 40 Dewey K G. Maternal body composition, caloric restriction and exercise during lactation.  J Nutr. 1998;  128 379S-380S
• 41 Luo S, Meier A H, Cincotta A H. Bromocriptine reduces obesity, glucose intolerance and extracellular monoamine metabolite levels in the ventromedial hypothalamus of Syrian hamsters.  Neuroendocrinology. 1998;  68 1-10
• 42 Hagan M M, Havel P J, Seeley R J, Woods S C, Ekhator N N, Baker D G, Hill K K, Wortman M D, Miller A H, Ronald L, Gingerich R L, Geracioti Jr T D. Cerebrospinal fluid and plasma leptin measurements: covariability with dopamine and cortisol in fasting humans.  Journal Of Clinical Endocrinology & Metabolism. 1999;  84 3579-3585
• 43 Aranda P, Sanchez L, Perez M D, Ena J M, Calvo M. Insulin in bovine colostrum and milk: evolution throughout lactation and binding to caseins.  J Dairy Sci. 1991;  74 4320-4325
• 44 Prosser C G, Fleet I R. Secretion of insulin-like growth factor II into milk.  Biochem Biophys Res Commun. 1992;  183 1230-1237
• 45 Prosser C G, Schwander J J. Influence of insulin-like growth factor-binding protein-2 on plasma clearance and transfer of insulin-like growth factors-I and -II from plasma into mammary-derived lymph and milk of goats.  Endocrinology. 1996;  150 121-127