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Prolactin Release Is Enhanced in Proportion to Excess Visceral Fat in Obese Women

Departments of General Internal Medicine (P.K., A.E.M., H.P.), Endocrinology and Metabolic Diseases (F.R.), and Clinical Chemistry (M.F.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: Dr. Hanno Pijl, Leiden University Medical Center, Department of Internal Medicine (C4-83), P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: h.pijl{at}lumc.nl.

	Abstract

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Prolactin (PRL) promotes (visceral) fat accrual in a variety of animal models. The release of PRL by the pituitary is tonically inhibited by dopamine through activation of the dopamine D2 receptor (D2R) of lactotroph cells, and obese humans appear to have reduced D2R-binding sites in their brain. Therefore, we hypothesized that spontaneous PRL release is enhanced in obese humans. To evaluate this hypothesis, we measured 24-h plasma PRL concentrations at 10-min intervals in 11 obese premenopausal women [body mass index (BMI), 33.3 ± 0.7 kg/m²] and 10 lean premenopausal women of similar age (BMI, 21.2 ± 0.6 kg/m²). Total body fat was determined using dual energy x-ray absorptiometry, and sc and visceral fat area was measured by magnetic resonance imaging in 10 obese subjects. PRL secretion rate was estimated by deconvolution analysis. All subjects were studied in the early follicular stage of their menstrual cycle. PRL secretion was significantly enhanced in obese women (total daily release, 137 ± 8; lean controls, 92 ± 8 µg/liter·24 h; P = 0.001) in proportion to their BMI (r² = 0.55; P < 0.001). Interestingly, PRL release was particularly associated with the size of the visceral fat mass (total PRL secretion vs. visceral fat area, r² = 0.64; P = 0.006). These data show that spontaneous PRL release is considerably enhanced in obese women in proportion to the size of their visceral fat mass. Because PRL is inhibited by D2R activation we speculate that elevated PRL secretion may be due to reduced D2R availability in the brain.

	Introduction

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PROLACTIN (PRL) IS an extremely versatile hormone that, among many other biological actions, affects energy balance and fuel metabolism. It stimulates food intake and fat deposition in female rats and birds and has lipogenic effects in hepatocytes (for review see Ref.1). Moreover, PRL receptor knockout mice have considerably reduced fat mass, where visceral fat is particularly diminished (2).

Lactotrophs have a high intrinsic basal secretory activity, and tonic inhibition by dopaminergic input via the dopamine D2 receptor (D2R) is required for maintenance of low circulating PRL levels (3). Thus, the D2R is instrumental in the control of PRL secretion. Experimental studies suggest that the number of D2R is reduced in the brain of a variety of obese animal models, and D2R activation reduces body weight in these rodents (4). Also, it appears that the availability of D2R-binding sites in striatal nuclei of obese humans is considerably reduced in proportion to their body mass index (BMI) (5). Therefore, we hypothesized that spontaneous PRL release is enhanced in obese humans, which then might modulate glucose and lipid metabolism to promote fat accrual. To test this postulate, we measured spontaneous 24-h PRL secretion in obese premenopausal women and compared various features of PRL release (estimated by deconvolution analysis) with those obtained in a control group of similar age and sex.

	Subjects and Methods

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Subjects

Eleven healthy obese premenopausal women (BMI, >30 kg/m²) and 10 lean (BMI, <25 kg/m²) controls of similar sex and age were recruited through advertisements in local news papers. The obese subjects were recruited so as to vary widely with respect to girth, whereas their BMIs were required to fall within a relatively narrow range to be able to specifically judge the effect of body fat distribution on hormone release. All participants were required to have regular menstrual cycles. Smoking and use of medication or oral contraceptives were exclusion criteria. Chronic disease was excluded by medical history, physical examination, and routine biochemical/hematological laboratory tests. All subjects gave written acknowledgment of informed consent for participation.

Clinical protocol

The protocol was approved by the medical ethics committee of the Leiden University Medical Center. All subjects were admitted to the Clinical Research Unit of the Department of General Internal Medicine in the early follicular stage of their menstrual cycles. A cannula for blood sampling was inserted into an antecubital vein, and blood samples for basal parameters were withdrawn. The cannula was attached to a three-way stopcock and was kept patent by a continuous saline infusion. Blood samples were taken with S-monovetten (Sarstedt, Etten-Leur, The Netherlands). One hour after admission, 24-h blood sampling started, and blood was collected at 10-min intervals. Subjects remained recumbent, except for bathroom visits. Meals were served according to a fixed time schedule. Vital signs were recorded at regular time intervals during the day. Lights were switched off at 2300 h. We did not register sleeping episodes by electroencephalogram during the 24-h blood samplings. However, great care was taken not to disturb patients while sampling blood during their sleep.

Body fat distribution

Total amount and location of excess body fat mass were determined in the obese women only. Total body fat mass was quantified using dual energy x-ray absorptiometry (6). Visceral and sc adipose tissue areas were assessed in the obese women by magnetic resonance imaging (MRI) as described previously, using a multislice, fast spin echo sequence (Gyroscan-T5 whole body scanner 0.5 Tesla, Philips Medical Systems, Best, The Netherlands) (7). Unfortunately, MRI imaging was impossible in one participant because of claustrophobia. MRI images were analyzed independently by two observers.

Assays

Each tube, except the serum tubes, was immediately chilled on ice. Samples were centrifuged at 4000 rpm at 4 C for 20 min within 60 min of sampling. Subsequently, plasma was divided into separate aliquots and frozen at –80 C until assays were performed. Basal free T₄ concentrations were estimated using electrochemiluminescence immunoassay (Roche Diagnostics Nederland BV, Almere, The Netherlands), and estradiol was determined by RIA (Diagnostic Systems Laboratory, Webster, TX). Plasma PRL concentrations were measured with a sensitive time-resolved fluoroimmunoassay with a detection limit of 0.04 µg/liter (Delfia, Wallac Oy, Turku, Finland). The PRL immunofluorometric assay was calibrated against the Third WHO standard 84/500 (1 ng/ml = 36 mU/liter). The intraassay coefficient of variation varies from 3.0–5.2%, and the interassay coefficient of variation ranges from 3.4–6.2%, in the concentration range from 0.1–250 µg/liter.

Calculations and statistics

Cluster. The Cluster program describes various characteristics of pulsatile hormone concentration profiles (8). A concentration peak is defined as a significant increase in the test peak cluster vs. the test nadir cluster. We used a 2 x 1 cluster configuration (two samples in the test nadir and one in the test peak) and t statistics of 2.0 for significant up- and downstrokes in PRL levels to constrain the false positive rate of peak identification to less than 5% of signal-free noise. The locations and durations of all significant plasma hormone peaks were identified, and the following parameters were determined: mean PRL concentration, peak frequency, mean peak height (maximum value attained in the peak), peak amplitude (mean incremental peak height), incremental peak height as a percentage of nadir, mean peak area (above the baseline), and mean interpeak valley concentration (nadir).

Pulse. Deconvolution analysis estimates hormone secretion and clearance rates on the basis of hormone concentration time series. The Pulse algorithm is a waveform-independent deconvolution method that can be used for calculation of mean and basal secretion without specifying shape, number, or time of secretory events (9). The technique requires a priori specification of hormonal half-life in plasma. PRL disappearance from plasma is best described by a two-compartment model, characterized by a fast component half-life of 18.4 min and a slow component half-life of 139 min, where the fractional contribution of the slow component to the overall decay amounts to 49.5% (10). Pulse quantifies 24-h basal and pulsatile hormone secretion. Total daily production is the sum of basal and pulsatile release.

Approximate entropy (ApEn). ApEn is a scale- and model-independent statistic that assigns a nonnegative number to time series data, reflecting the regularity of these data (11). We used normalized ApEn parameters of m = 1, r = 20%, and 1000 for the number of runs to test for regularity in 24-h plasma PRL concentrations, as described previously (12). Hence, this member of the ApEn family is designated ApEn (1, 20%). The ApEn metric evaluates the consistency of recurrent subordinate (nonpulsatile) patterns in a time series and thus yields information distinct from and complementary deconvolution (pulse) analyses (13). Higher absolute ApEn values denote greater relative randomness of hormone patterns. Data are presented as normalized ApEn ratios, defined by the mean ratio of absolute ApEn to that of 1000 randomly shuffled versions of the same series.

Cosinor. Cosinor analysis entails trigonometric regression of a cosine function on the full 24-h plasma hormone concentration profile vs. time. Cosinor analysis was used to define the acrophase (clock time during 24 h at which PRL concentration is maximal) of the plasma PRL concentration profile.

Statistical analysis

Means of PRL secretion parameters of both groups were compared using nonpaired two-tailed independent t test. The significance level was set at 0.05. Data are presented as the mean ± SEM unless otherwise specified. Pearson’s correlation analysis was used to determine the association between BMI and various features of pulsatile PRL secretion in obese and normal weight women. Univariate analysis was used to describe the relationship between various specific anthropometric measures (percent body fat (%BF), sc fat mass (SFM), and visceral fat mass (VFM)) and PRL secretion parameters in the obese subjects only.

	Results

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Subjects

Eleven obese and 10 lean subjects were enrolled in this study. The mean age was similar in both groups (obese, 38.1 ± 2.1; lean, 32.7 ± 2.7 yr; P = 0.128), whereas BMI was significantly different (obese, 33.3 ± 0.7; lean, 21.2 ± 0.6 kg/m²; P < 0.001).

All subjects were clinically euthyroid, and T₄ levels were within the normal range in the obese and lean subjects. We did not find significant differences between mean basal estradiol levels (obese, 169 ± 32; lean, 197 ± 55 pmol/liter; P = 0.637).

Plasma PRL concentration profiles

Mean 24-h PRL concentration, peak amplitude, peak width, peak area, and peak height were significantly higher, whereas peak frequency was significantly lower, in obese subjects compared with lean controls (Table 1).

The regularity of 24-h plasma PRL concentration-time series, as determined by the ApEn statistic, was similar in obese vs. lean subjects (0.47 ± 0.03 vs. 0.50 ± 0.05, respectively; P = 0.616).

Acrophase of plasma PRL concentration-time series

The acrophase of the nyctohemeral PRL rhythm, which is characterized by a cosine wave, occurred in the early morning in obese and lean subjects at comparable clock times (obese, 0431 h ± 87 min; lean, 0653 h ± 111 min; P = 0.330).

Features of PRL secretion

Both basal and pulsatile PRL secretion rates were clearly higher in obese subjects; basal release (as a fraction of total secretion) was particularly enhanced (Table 2). Graphical illustrations of representative plots of 24-h plasma PRL concentration patterns in two obese subjects and age-matched lean controls are shown in Fig. 1.

View larger version (17K): [in this window] [in a new window]   FIG. 1. Serum PRL concentration-time series in two obese subjects (•) and two control subjects (). Data reflect sampling of blood every 10 min for 24 h. Sampling starts at 1800 h. The age of the women in the left panel was 33 yr, and the BMIs were 20.6 and 31.0 kg/m2. The age of the women in the right panel was 48 yr, and the BMIs were 21.5 and 32.3 kg/m2.

Both obese and lean subjects were included in correlation analyses of BMI vs. PRL concentration parameters. BMI was positively associated with mean 24-h plasma PRL concentration, peak amplitude, peak width, peak area, and maximum peak height, whereas an inverse linear relationship was found between BMI and plasma concentration peak frequency (Table 3). Basal, pulsatile, and total PRL secretion rates were also strongly positively correlated with BMI (Table 3 and Fig. 2).

View larger version (11K): [in this window] [in a new window]   FIG. 2. Left panel, Linear correlation between BMI and the 24-h PRL secretion rate in 11 obese women and 10 lean women. The PRL secretion rate was calculated by deconvolution analysis of the plasma concentration profile, obtained by 10-min blood sampling over 24 h. Right panel, Linear correlation between VFM and PRL secretion rate in 10 obese subjects.

Pearson’s correlations between measures of BF mass and distribution (% BF, VFM, and SFM) and various features of PRL release were estimated in 10 obese subjects only (MRI could not be performed in one subject because of her claustrophobia). Univariate analysis revealed that PRL secretion rates were specifically associated with the size of the visceral fat depot (Table 4 and Fig. 2), whereas the % BF and sc fat area were not significantly associated with features of PRL release (Table 4).

	Discussion

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Several previous papers report that basal (single measurement) PRL levels are similar in obese and normal weight humans, whereas PRL release in response to a number of secretagogues was blunted in obese individuals compared with lean controls (14, 15, 16, 17, 18, 19, 20, 21, 22). Moreover, 24-h integrated plasma PRL levels (measured hourly) were not significantly different in obese and normal weight humans in one earlier study (23). Our findings are in apparent conflict with these observations. However, as far as we are aware, spontaneous PRL release, calculated by deconvolution analysis from frequently sampled plasma hormone time series data, has never previously been quantified in obese humans. Blood sampling at short time intervals is required to adequately detect high frequency variations in PRL plasma concentrations. Single or even hourly PRL measurements are not likely to accurately reflect spontaneous PRL secretion given the pulsatile nature of its release process. Other factors that may explain the difference between our study and previous ones pertain to the subjects included and the design of the studies. For example, both men and women of varying ages were enrolled in the study that measured hourly PRL concentrations; the women were both pre- and postmenopausal, and premenopausal women were studied at different stages of their menstrual cycle. In addition, various factors act in concert to orchestrate PRL secretion by the pituitary gland. A number of (putative) positive feedforward signals (e.g. TRH) interact with inhibitory inputs (primarily dopamine via the D2R) and direct negative feedback restraint by PRL itself to generate a pulsatile release profile. In this context, it is conceivable that enhanced spontaneous PRL secretion (our study) dampens secretagogue-induced PRL release (14, 17, 18, 19, 20, 21, 22) via strengthened negative feedback in obese humans.

PRL is an extremely versatile hormone that plays a role in the regulation of carbohydrate and lipid metabolism in a variety of species. In fish, birds, and rodents, PRL promotes fat storage through stimulation of food intake and multiple metabolic routes (1), and knockout of the PRL receptor gene in mice causes loss of body fat, primarily from the visceral depot (2). The latter observation agrees with our data, in that PRL release in our subjects was particularly associated with the size of their visceral fat area. Humans with prolactinoma tend to be obese and lose weight once treated effectively (with D2R agonists) (24, 25). Activation of the D2R is the major route to suppress pituitary PRL release. D2R antagonism in the treatment of schizophrenia enhances circulating PRL levels and causes weight gain in a very high percentage of patients (26, 27, 28). Interestingly, Wang et al. (5) showed that the number of D2R-binding sites in the brain of obese humans is strongly reduced and inversely associated with BMI. Collectively, current perceptions are in keeping with the postulate that PRL may be one of the endocrine messengers that relay reduced D2R-mediated dopaminergic neural signals to peripheral tissues to promote (visceral) fat storage. However, it clearly requires further investigation to establish whether dopaminergic mechanisms indeed underlie enhanced PRL release in obese humans, because D2R activity was not addressed directly in this study.

Although the above data provide evidence to the contrary, we cannot rule out that enhanced PRL release was a consequence of obesity in our subjects. For example, circulating leptin levels are increased in obese humans (29, 30), and leptin stimulates PRL secretion in vitro in pituitary lactotrophs and has a stimulatory effect on steroid-induced and spontaneous PRL secretion in rats (31, 32). Thus, hyperleptinemia (as a corollary of obesity) may promote PRL release in obese humans.

In conclusion, we show that PRL secretion is enhanced in obese premenopausal women. Total daily release is strongly associated with BMI, in particular with the size of the visceral fat depot. We speculate that enhanced PRL secretion may be a mechanistic link between reduced D2R availability in the brain and (visceral) obesity.

	Footnotes

 
Abbreviations: ApEn, Approximate entropy; % BF, percent body fat; BMI, body mass index; D2R, dopamine D2 receptor; MRI, magnetic resonance imaging; PRL, prolactin; SFM, sc fat mass; VFM, visceral fat mass.

Received December 23, 2003.

Accepted June 9, 2004.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA 1998 Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268[Abstract/Free Full Text]
2. Freemark M, Fleenor D, Driscoll P, Binart N, Kelly P 2001 Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology 142:532–537[Abstract/Free Full Text]
3. Ben Jonathan N, Hnasko R 2001 Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 22:724–763[Abstract/Free Full Text]
4. Pijl H 2003 Reduced dopaminergic tone in hypothalamic neural circuits: expression of a "thrifty" genotype underlying the metabolic syndrome? Eur J Pharmacol 480:125–31[CrossRef][Medline]
5. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS 2001 Brain dopamine and obesity. Lancet 357:354–357[CrossRef][Medline]
6. Blake GM, Fogelman I 1997 Technical principles of dual energy x-ray absorptiometry. Semin Nucl Med 27:210–228[CrossRef][Medline]
7. Langendonk JG, Pijl H, Toornvliet AC, Burggraaf J, Frolich M, Schoemaker RC, Doornbos J, Cohen AF, Meinders AE 1998 Circadian rhythm of plasma leptin levels in upper and lower body obese women: influence of body fat distribution and weight loss. J Clin Endocrinol Metab 83:1706–1712[Abstract/Free Full Text]
8. Veldhuis JD, Johnson ML 1986 Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol 250:E486–E493
9. Johnson ML, Veldhuis JD 1995 Evolution of deconvolution analysis as a hormone pulse detection period. Methods Neurosci 28:1–24
10. Sievertsen GD, Lim VS, Nakawatase C, Frohman LA 1980 Metabolic clearance and secretion rates of human prolactin in normal subjects and in patients with chronic renal failure. J Clin Endocrinol Metab 50:846–852[Abstract/Free Full Text]
11. Pincus SM, Keefe DL 1992 Quantification of hormone pulsatility via an approximate entropy algorithm. Am J Physiol 262:E741–E754
12. Groote VR, van den BG, Pincus SM, Frolich M, Veldhuis JD, Roelfsema F 1999 Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas. Eur J Endocrinol 140:192–200[Abstract]
13. Veldhuis JD, Pincus SM 1998 Orderliness of hormone release patterns: a complementary measure to conventional pulsatile and circadian analyses. Eur J Endocrinol 138:358–362[CrossRef][Medline]
14. Bernini GP, Lucarini AR, Vivaldi MS, Del Corso C, Lenzi M, Salvetti A 1989 Naloxone does not antagonize the antihypertensive effect of chronic captopril therapy in hypertensive patients. Cardiovasc Drugs Ther 3:829–833[CrossRef][Medline]
15. Kopelman PG, White N, Pilkington TR, Jeffcoate SL 1979 Impaired hypothalamic control of prolactin secretion in massive obesity. Lancet 1:747–750[Medline]
16. Rojdmark S, Berg A, Rossner S, Wetterberg L 1991 Nocturnal melatonin secretion in thyroid disease and in obesity. Clin Endocrinol (Oxf) 35:61–65[Medline]
17. Rojdmark S, Rossner S 1991 Decreased dopaminergic control of prolactin secretion in male obesity: normalization by fasting. Metabolism 40:191–195[CrossRef][Medline]
18. Weaver JU, Noonan K, Kopelman PG 1991 An association between hypothalamic-pituitary dysfunction and peripheral endocrine function in extreme obesity. Clin Endocrinol (Oxf) 35:97–102[Medline]
19. Papalia D, Lunetta M, Di Mauro M 1989 Effects of naloxone on prolactin, growth hormone and cortisol response to insulin hypoglycemia in obese subjects. J Endocrinol Invest 12:777–782[Medline]
20. Bernini GP, Argenio GF, Vivaldi MS, Del Corso C, Sgro M, Franchi F, Luisi M 1989 Effects of fenfluramine and ritanserin on prolactin response to insulin-induced hypoglycemia in obese patients: evidence for failure of the serotoninergic system. Horm Res 31:133–137[CrossRef][Medline]
21. Altomonte L, Zoli A, Alessi F, Ghirlanda G, Manna R, Greco AV 1987 Effect of fenfluramine on growth hormone and prolactin secretion in obese subjects. Horm Res 27:190–194[CrossRef][Medline]
22. Amatruda JM, Hochstein M, Hsu TH, Lockwood DH 1982 Hypothalamic and pituitary dysfunction in obese males. Int J Obes 6:183–189[Medline]
23. Cavagnini F, Maraschini C, Pinto M, Dubini A, Polli EE 1981 Impaired prolactin secretion in obese patients. J Endocrinol Invest 4:149–153[Medline]
24. Copinschi G, De Laet MH, Brion JP, Leclercq R, L’Hermite M, Robyn C, Virasoro E, Van Cauter E 1978 Simultaneous study of cortisol, growth hormone and prolactin nyctohemeral variations in normal and obese subjects. Influence of prolonged fasting in obesity. Clin Endocrinol (Oxf) 9:15–26[Medline]
25. Doknic M, Pekic S, Zarkovic M, Medic-Stojanoska M, Dieguez C, Casanueva F, Popovic V 2002 Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine. Eur J Endocrinol 147:77–84[Abstract]
26. Greenman Y, Tordjman K, Stern N 1998 Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol (Oxf) 48:547–553[CrossRef][Medline]
27. Casey DE 1996 Side effect profiles of new antipsychotic agents. J Clin Psychiatry 57:40–45
28. Hummer M, Kemmler G, Kurz M, Kurzthaler I, Oberbauer H, Fleischhacker WW 1995 Weight gain induced by clozapine. Eur Neuropsychopharmacol 5:437–440[CrossRef][Medline]
29. Baptista T, Alastre T, Contreras Q, Martinez JL, Araujo de Baptista E, Paez X, Hernandez L 1997 Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy men: relationship with body weight regulation. Pharmacopsychiatry 30:250–255[Medline]
30. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL 1996 Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295[Abstract/Free Full Text]
31. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S 1995 Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155–1161[CrossRef][Medline]
32. Watanobe H, Suda T, Wikberg JE, Schioth HB 1999 Evidence that physiological levels of circulating leptin exert a stimulatory effect on luteinizing hormone and prolactin surges in rats. Biochem Biophys Res Commun 263:162–165[CrossRef][Medline]

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This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kok, P. Articles by Pijl, H. Search for Related Content PubMed PubMed Citation Articles by Kok, P. Articles by Pijl, H.