Skip to main content
Top
Published in: Endocrine 2/2022

01-05-2022 | Progesterone | Original Article

Maternal serum leptin in the pregnant rat: fetal-placental implantation number and progesterone

Authors: George M. Butterstein, Colin Hirst, V. Daniel Castracane

Published in: Endocrine | Issue 2/2022

Login to get access

Abstract

Purpose

This study was designed to determine whether there is a role of the placenta in the regulation of maternal serum leptin levels in the pregnant rat.

Methods

We have adjusted the number of fetal-placental implants on day 9 in the pregnant rat by aspirating fetal-placental units to adjust the number to 1–2, 4–5 per rat or >10 in controls. Serum levels of leptin and progesterone were determined by radioimmunoassay. A separate group of pregnant rats were ovariectomized and maintained with progesterone silastic capsules (10, 20 or 40 mm).

Results

In the pregnant rats with varied fetal-placental implant numbers, the maternal serum leptin were greatest in the group with the smallest number (1–2) of implants; intermediate in the midgroup (4–5 implants); and lowest in the group with a full complement of implantations (>10) (p < 0.001). Serum progesterone levels are lowest in the 1–2 implantation group. In the ovariectomized rats there was a stepwise decline in serum leptin (p < 0.05) as the dose of progesterone increased (p < 0.01). Both of these studies suggest that progesterone suppressed maternal serum leptin levels.

Conclusions

Increasing placental mass is not associated with increasing maternal serum leptin levels in the pregnant rat; the contrary condition is observed with the least placental implants having the highest leptin levels. Progesterone seems to suppress serum leptin levels in several physiological models.
Literature
1.
go back to reference Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, J.M. Friedman, Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994)CrossRef Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, J.M. Friedman, Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994)CrossRef
2.
go back to reference T. Tomimatsu, M. Yamaguchi, T. Murakami, K. Ogura, M. Sakata, N. Mitsuda, T. Kanzaki, H. Kurachi, M. Irahara, A. Miyake et al. Increase of mouse leptin production by adipose tissue after midpregnancy: gestational profile of serum leptin concentration. Biochem. Biophys. Res. Comm. 240, 213–215 (1997)CrossRef T. Tomimatsu, M. Yamaguchi, T. Murakami, K. Ogura, M. Sakata, N. Mitsuda, T. Kanzaki, H. Kurachi, M. Irahara, A. Miyake et al. Increase of mouse leptin production by adipose tissue after midpregnancy: gestational profile of serum leptin concentration. Biochem. Biophys. Res. Comm. 240, 213–215 (1997)CrossRef
3.
go back to reference M. Kawai, M. Yamaguchi, T. Murakami, K. Shima, Y. Murata, K. Kishi, The placenta is not the main source of leptin production in pregnant rat: Gestational profile of leptin in plasma and adipose tissue. Biochem. Biophys. Res. Comm. 240, 798–802 (1997)CrossRef M. Kawai, M. Yamaguchi, T. Murakami, K. Shima, Y. Murata, K. Kishi, The placenta is not the main source of leptin production in pregnant rat: Gestational profile of leptin in plasma and adipose tissue. Biochem. Biophys. Res. Comm. 240, 798–802 (1997)CrossRef
4.
go back to reference L. Hardie, P. Trayhurn, D. Abramovich, P. Fowler, Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin. Endocrinol. 47, 101–106 (1997)CrossRef L. Hardie, P. Trayhurn, D. Abramovich, P. Fowler, Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy. Clin. Endocrinol. 47, 101–106 (1997)CrossRef
5.
go back to reference T.J. Highman, J.E. Friedman, L.P. Huston, W.W. Wong, P.M. Catalano, Longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate in pregnancy. Am. J. Obstet. Gynecol. 178, 1010–1015 (1998)CrossRef T.J. Highman, J.E. Friedman, L.P. Huston, W.W. Wong, P.M. Catalano, Longitudinal changes in maternal serum leptin concentrations, body composition, and resting metabolic rate in pregnancy. Am. J. Obstet. Gynecol. 178, 1010–1015 (1998)CrossRef
6.
go back to reference R. Senaris, T. Garcia-Caballero, X. Casabiell, R. Gallego, R. Castro, R.V. Considine, C. Dieguez, F.F. Casanueva, Synthesis of leptin in human placenta. Endocrinology 138, 4501–4504 (1997)CrossRef R. Senaris, T. Garcia-Caballero, X. Casabiell, R. Gallego, R. Castro, R.V. Considine, C. Dieguez, F.F. Casanueva, Synthesis of leptin in human placenta. Endocrinology 138, 4501–4504 (1997)CrossRef
7.
go back to reference H. Masuzaki, Y. Ogawa, N. Sagawa, K. Hosoda, T. Matsumoto, H. Mise, H. Nishimura, Y. Yoshimasa, I. Tanaka, T. Mori et al. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat. Med. 3, 1029–1033 (1997)CrossRef H. Masuzaki, Y. Ogawa, N. Sagawa, K. Hosoda, T. Matsumoto, H. Mise, H. Nishimura, Y. Yoshimasa, I. Tanaka, T. Mori et al. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat. Med. 3, 1029–1033 (1997)CrossRef
8.
go back to reference J.A. Amico, A. Thomas, R.S. Crowley, L.A. Burmeister, Concentrations of leptin in the serum of pregnant, lactating and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue. Life Sci. 63, 1387–1395 (1998)CrossRef J.A. Amico, A. Thomas, R.S. Crowley, L.A. Burmeister, Concentrations of leptin in the serum of pregnant, lactating and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue. Life Sci. 63, 1387–1395 (1998)CrossRef
9.
go back to reference M.D. Garcia, F.F. Casanueva, C. Dieguez, R.M. Senaris, Gestational profile of leptin messenger ribonucleic acid (mRNA) content in the placenta and adipose tissue in the rat, and regulation of the mRNA levels of the leptin receptor subtypes in the hypothalamus during pregnancy and lactation. Biol. Reprod. 62, 698–703 (2000)CrossRef M.D. Garcia, F.F. Casanueva, C. Dieguez, R.M. Senaris, Gestational profile of leptin messenger ribonucleic acid (mRNA) content in the placenta and adipose tissue in the rat, and regulation of the mRNA levels of the leptin receptor subtypes in the hypothalamus during pregnancy and lactation. Biol. Reprod. 62, 698–703 (2000)CrossRef
10.
go back to reference R.M. Seeber, J.T. Smith, B.J. Waddell, Plasma leptin-binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat. Biol. Reprod. 66, 1762–1767 (2002)CrossRef R.M. Seeber, J.T. Smith, B.J. Waddell, Plasma leptin-binding activity and hypothalamic leptin receptor expression during pregnancy and lactation in the rat. Biol. Reprod. 66, 1762–1767 (2002)CrossRef
11.
go back to reference B.J. Waddell and J.T. Smith, Leptin in rodent pregnancy. In: Leptin and Reproduction, ed by M.C. Henson, V.D. Castracane. (Kluwer Academic/Plenum Publishers, New York, 2003), p. 221–237. B.J. Waddell and J.T. Smith, Leptin in rodent pregnancy. In: Leptin and Reproduction, ed by M.C. Henson, V.D. Castracane. (Kluwer Academic/Plenum Publishers, New York, 2003), p. 221–237.
12.
go back to reference C.J. Ashworth, N. Hoggard, L. Thomas, J.G. Mercer, J.M. Wallace, R.G. Lea, Placental leptin. Rev. Reprod. 5, 18–24 (2000)CrossRef C.J. Ashworth, N. Hoggard, L. Thomas, J.G. Mercer, J.M. Wallace, R.G. Lea, Placental leptin. Rev. Reprod. 5, 18–24 (2000)CrossRef
13.
go back to reference J. Zhao, T.H. Kunz, N. Tumba, L.C. Schulz, C. Li, M. Reeves, E. Widmaier, Comparative analysis of expression and secretion of placental leptin in mammals. Am. J. Physiol. Integr. Comp. Physiol. 285, R438–R446 (2003)CrossRef J. Zhao, T.H. Kunz, N. Tumba, L.C. Schulz, C. Li, M. Reeves, E. Widmaier, Comparative analysis of expression and secretion of placental leptin in mammals. Am. J. Physiol. Integr. Comp. Physiol. 285, R438–R446 (2003)CrossRef
14.
go back to reference N. Hoggard, J. Crabtree, S. Allstaff, D.R. Abramovich, P. Haggarty, Leptin secretion to both maternal and fetal circulation in the ex vivo perfused human term placenta. Placenta 22, 347–352 (2001)CrossRef N. Hoggard, J. Crabtree, S. Allstaff, D.R. Abramovich, P. Haggarty, Leptin secretion to both maternal and fetal circulation in the ex vivo perfused human term placenta. Placenta 22, 347–352 (2001)CrossRef
15.
go back to reference K. Linneman, A. Malek, R. Sager, W.F. Blum, H. Schneider, C. Fusch, Leptin production and release in the dually in vitro perfused human placenta. J. Clin. Endocrinol. Metab. 85, 4298–4301 (2001) K. Linneman, A. Malek, R. Sager, W.F. Blum, H. Schneider, C. Fusch, Leptin production and release in the dually in vitro perfused human placenta. J. Clin. Endocrinol. Metab. 85, 4298–4301 (2001)
16.
go back to reference M.C. Henson, K.F. Swan, J.S. O’Neil, Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term. Obstet. Gynecol. 92, 1020–1028 (1998)PubMed M.C. Henson, K.F. Swan, J.S. O’Neil, Expression of placental leptin and leptin receptor transcripts in early pregnancy and at term. Obstet. Gynecol. 92, 1020–1028 (1998)PubMed
17.
go back to reference J.S. O’Neil, A.E. Green, D.E. Edwards, K.F. Swan, T. Gimpel, V.D. Castracane, M.C. Henson, Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy. J. Clin. Endocrinol. Metab. 86, 2518–2524 (2001)CrossRef J.S. O’Neil, A.E. Green, D.E. Edwards, K.F. Swan, T. Gimpel, V.D. Castracane, M.C. Henson, Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy. J. Clin. Endocrinol. Metab. 86, 2518–2524 (2001)CrossRef
18.
go back to reference R.S. Brogan, S.E. Mitchell, P. Trayhurn, M.S. Smith, Suppression of leptin during lactation: contribution of the suckling stimulus versus milk production. Endocrinology 140, 2621–2627 (1999)CrossRef R.S. Brogan, S.E. Mitchell, P. Trayhurn, M.S. Smith, Suppression of leptin during lactation: contribution of the suckling stimulus versus milk production. Endocrinology 140, 2621–2627 (1999)CrossRef
19.
go back to reference S.R. Ladyman, Leptin resistance during pregnancy in the rat. J. Neuroendocrinol. 20, 269–277 (2008)CrossRef S.R. Ladyman, Leptin resistance during pregnancy in the rat. J. Neuroendocrinol. 20, 269–277 (2008)CrossRef
20.
go back to reference R.A. Augustine, S.R. Ladyman, D.R. Grattan, From feeding one to feeding many: hormone-induced changes in bodyweight homeostasis during pregnancy. J. Physiol. 582, 387–397 (2008)CrossRef R.A. Augustine, S.R. Ladyman, D.R. Grattan, From feeding one to feeding many: hormone-induced changes in bodyweight homeostasis during pregnancy. J. Physiol. 582, 387–397 (2008)CrossRef
21.
go back to reference R.G.P. Denis, G. Williams, R.G. Vernon, Regulation of serum leptin and its role in the hyperphagia of lactation in the rat. J. Endocrinol. 176, 193–203 (2003)CrossRef R.G.P. Denis, G. Williams, R.G. Vernon, Regulation of serum leptin and its role in the hyperphagia of lactation in the rat. J. Endocrinol. 176, 193–203 (2003)CrossRef
22.
go back to reference H. Kato, W.K. Morishige, I. Rothchild, A quantitative relation between experimentally determined number of conceptuses and corpus luteum activity in the pregnant rat. Endocrinology 105, 846–850 (1979)CrossRef H. Kato, W.K. Morishige, I. Rothchild, A quantitative relation between experimentally determined number of conceptuses and corpus luteum activity in the pregnant rat. Endocrinology 105, 846–850 (1979)CrossRef
23.
go back to reference V.D. Castracane, J.L. DeLa Cruz, The relationship of conceptus number and fetal sex to maternal serum testosterone concentration in the rat. Proc. Soc. Exp. Biol. Med. 195, 109–113 (1990)CrossRef V.D. Castracane, J.L. DeLa Cruz, The relationship of conceptus number and fetal sex to maternal serum testosterone concentration in the rat. Proc. Soc. Exp. Biol. Med. 195, 109–113 (1990)CrossRef
24.
go back to reference R. Coya, P. Martul, J. Algorta, M.A. Aniel-Quiroga, M.A. Busturia, R. Senaris, Progesterone and human placental lactogen inhibit leptin secretion on cultured trophoblast cells from human placentas at term. Gynecol. Endocrinol. 21, 27–32 (2005)CrossRef R. Coya, P. Martul, J. Algorta, M.A. Aniel-Quiroga, M.A. Busturia, R. Senaris, Progesterone and human placental lactogen inhibit leptin secretion on cultured trophoblast cells from human placentas at term. Gynecol. Endocrinol. 21, 27–32 (2005)CrossRef
25.
go back to reference M. Abelenda, M. Puerta, Leptin release is decreased in white adipocytes isolated from progesterone-treated rats. Endocr. Res. 30, 335–342 (2004)CrossRef M. Abelenda, M. Puerta, Leptin release is decreased in white adipocytes isolated from progesterone-treated rats. Endocr. Res. 30, 335–342 (2004)CrossRef
26.
go back to reference H. Watanobe, T. Suda, A detailed study on the role of sex steroid milieu in determining plasma leptin concentrations in adult male and female rats. Biochem. Biophys. Res. Comm. 259, 56–59 (1999)CrossRef H. Watanobe, T. Suda, A detailed study on the role of sex steroid milieu in determining plasma leptin concentrations in adult male and female rats. Biochem. Biophys. Res. Comm. 259, 56–59 (1999)CrossRef
27.
go back to reference A. Jelks, L. Belkacemi, G. Han, W.-L. Chong, M.G. Ross, M. Desai, Paradoxical increase in maternal plasma leptin levels in food-restricted gestation: contribution by placental and adipose tissue. Reprod. Sci. 16, 665–675 (2009)CrossRef A. Jelks, L. Belkacemi, G. Han, W.-L. Chong, M.G. Ross, M. Desai, Paradoxical increase in maternal plasma leptin levels in food-restricted gestation: contribution by placental and adipose tissue. Reprod. Sci. 16, 665–675 (2009)CrossRef
28.
go back to reference L.E. Moore, K.L. Wallace, B.T. Alexander, W.L. May, B.D. Thigpen, W.A. Bennett, Reduced placental perfusion causes an increase in maternal serum leptin. Placenta 24, 877–881 (2003)CrossRef L.E. Moore, K.L. Wallace, B.T. Alexander, W.L. May, B.D. Thigpen, W.A. Bennett, Reduced placental perfusion causes an increase in maternal serum leptin. Placenta 24, 877–881 (2003)CrossRef
29.
go back to reference G.M. Butterstein, J.H. Leathem, Placental growth modification during pregnancy in the rat. Endocrinology 95, 645–649 (1974)CrossRef G.M. Butterstein, J.H. Leathem, Placental growth modification during pregnancy in the rat. Endocrinology 95, 645–649 (1974)CrossRef
Metadata
Title
Maternal serum leptin in the pregnant rat: fetal-placental implantation number and progesterone
Authors
George M. Butterstein
Colin Hirst
V. Daniel Castracane
Publication date
01-05-2022
Publisher
Springer US
Keyword
Progesterone
Published in
Endocrine / Issue 2/2022
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-022-02984-2

Other articles of this Issue 2/2022

Endocrine 2/2022 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.