The inhibitory effect of progesterone on lactogenesis during pregnancy is already evident by mid- to late gestation in rodents

2012 ◽  
Vol 24 (5) ◽  
pp. 704 ◽  
Author(s):  
Constanza M. López-Fontana ◽  
María E. Maselli ◽  
Ana M. Salicioni ◽  
Rubén W. Carón
Keyword(s):  
Mammary Gland ◽  
Hormonal Regulation ◽  
Time Course ◽  
Mammary Epithelium ◽  
Secretory Activity ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Late Gestation ◽  
Pregnant Rats ◽  
Mammary Gland Morphology

Lactogenesis is a very complex process highly dependent on hormonal regulation. In the present study the time-course of the inhibitory actions of progesterone on prolactin secretion, mammary gland morphology and lactogenesis from mid- to late gestation in rodents was investigated. Groups of pregnant rats were luteectomised or administered with mifepristone on Day 10, 13, 15 or 17 of gestation and decapitated 28 or 48 h later. Whole-blood samples and the inguinal mammary glands were taken for determinations of hormone levels and for measurement of mammary content of casein and lactose and for tissue morphology analyses, respectively. Luteectomy or mifepristone evoked prolactin increases only after Day 17 of gestation. Mammary content of casein was increased by both treatments regardless of timing or duration. Mifepristone was less effective than luteectomy in inducing lactose production and the effect was only observed after Day 15 of gestation. Analysis of mammary gland morphology confirmed the observed effect of progesterone on lactogenesis. Both treatments triggered remarkable secretory activity in the mammary gland, even without a parallel epithelial proliferation, demonstrating that the mammary epithelium is able to synthesise milk compounds long before its full lobulo–alveolar development is achieved, provided that progesterone action is abolished. Thus, the present study demonstrates that progesterone is a potent hormonal switch for the prolactin and prolactin-like effects on mammary gland development and its milk-synthesising capacity during pregnancy, and that its inhibitory action is already evident by mid-pregnancy in rodents.

scholarly journals Hormonal regulation of retinoic acid-binding proteins in the mammary gland

1981 ◽  
Vol 200 (3) ◽  
pp. 591-595 ◽  
Author(s):  
R G Mehta ◽  
R C Moon
Keyword(s):  
Retinoic Acid ◽  
Mammary Gland ◽  
Protein Content ◽  
Hormonal Regulation ◽  
Protein Concentration ◽  
Mammary Glands ◽  
Pregnant Rats ◽  
Rab Protein ◽  
Low Concentrations ◽  
Retinoic Acid Binding Proteins

A cytosolic retinoic acid-binding (RAB) protein that sediments specifically as a 2S component on sucrose density gradients was detected in the mammary glands of virgin, pregnant and lactating rats. Mammary cytosol from pregnant rats contained significantly higher concentrations of cytosolic RAB protein than did cytosol from either virgin or lactating rats. The glands of pregnant animals exhibited increased concentration of cytosolic RAB protein during the first 5 days of pregnancy, and a steady decline was observed thereafter. The concentration of cytosolic RAB protein dropped to the value observed during lactation on the day 20 of pregnancy. Moreover, throughout lactation, low concentrations of cytosolic RAB protein were maintained. Daily treatment of virgin and lactating animals with 5 micrograms of oestradiol-17 beta for 1 week increased cytosolic RAB protein to concentrations comparable with those seen in pregnant rats. Progesterone, however, did not affect the mammary cytosolic RAB protein content of virgin rats. These results suggest hormonal involvement in the regulation of cytosolic RAB protein concentration of mammary gland during differentiation.

Systemic hemodynamics and oxygen transport during pregnancy in chronically instrumented, conscious rats

1992 ◽  
Vol 263 (6) ◽  
pp. H1911-H1918 ◽  
Author(s):  
G. J. Gilson ◽  
M. D. Mosher ◽  
K. P. Conrad
Keyword(s):  
Time Course ◽  
Carbon Dioxide Production ◽  
Respiratory Alkalosis ◽  
Late Gestation ◽  
Control Group ◽  
Peripheral Vascular ◽  
Pregnant Rats ◽  
Conscious Rats ◽  
Content Difference ◽  
Ultimate Purpose

Knowledge about possible alterations in cardiac output (CO), total peripheral vascular resistance (TPVR), and their time course and magnitude of change is conspicuously lacking for the conscious gravid rat. Therefore, we assessed CO using Fick methodology in unrestrained, chronically instrumented, conscious rats. The rats were studied during early (day 7), mid (day 13), or late gestation (day 18) along with nonpregnant control rats matched with respect to age and days postsurgery. Significant differences between pregnant and nonpregnant rats were observed during midgestation, when CO was increased by 26 +/- 12% and TPVR was decreased by 23 +/- 9% in the pregnant animals. These changes were accompanied by a narrowed arterial-mixed venous oxygen content difference (AVD; P < 0.05 vs. nonpregnant). In late gravid rats, CO was higher than nonpregnant values by 49 +/- 8%, and TPVR was lower by 34 +/- 7% (both P < 0.05). Oxygen consumption and carbon dioxide production were significantly increased, and AVD further narrowed when compared with the nonpregnant control group. With the exception of absent chronic respiratory alkalosis in pregnant rats, we conclude that cardiovascular and respiratory changes in conscious, gravid rats and in pregnant women are comparable. We speculate that the ultimate purpose of many of these adaptations is to increase CO so that oxygen delivery and the supply of nutrients to the uteroplacental units are sufficient or more than sufficient to meet oxygen and nutrient demands. At midgestation, the rise in CO seems to anticipate the oxygen needs of the nascent uteroplacental units.

Effects of two enkephalin analogues, morphine sulphate, dopamine and naloxone on prolactin secretion from rat anterior pituitary glands in vitro

1986 ◽  
Vol 109 (3) ◽  
pp. 313-320 ◽  
Author(s):  
A. M. Bentley ◽  
M. Wallis
Keyword(s):  
Anterior Pituitary ◽  
Time Course ◽  
Opiate Receptors ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Prolactin Secretion ◽  
Morphine Sulphate ◽  
Low Concentrations ◽  
Pituitary Glands

ABSTRACT Experiments were carried out on the antagonistic effects of opiates on the inhibition by dopamine of prolactin secretion from rat anterior pituitary glands. Dose–response and time-course experiments were carried out using both static incubation of paired hemipituitary glands and perifusion of whole glands. Dopamine (10–1000 nmol/l) was found to have an inhibitory effect on prolactin secretion, but at a lower concentration (0·1 nmol/l) a small stimulation was observed. Against an inhibition established with 100 nmol dopamine/l in static incubation, the three opiates under study, morphine sulphate, Leu5enkephalin and d-Ala2,Met5-enkephalin (DAME), had a maximum antagonistic effect at 50–1000 nmol/l in a 90-min incubation. Morphine and DAME were rather more effective than Leu5-enkephalin, possibly because of degradation of the latter. Naloxone reversed the effect of morphine. All three opiates showed little effect on dopamine-inhibited prolactin secretion in a perifusion system. The data accord with previous suggestions that prolactin secretion may be stimulated both by very low concentrations of dopamine and by opiates acting to reverse the inhibition exerted by higher dopamine concentrations. It should be noted that both morphine and the enkephalins have similar effects on prolactin secretion, despite their normal specificity for different opiate receptors; their actions on the pituitary may thus be rather non-specific. J. Endocr. (1986) 109, 313–320

Differential effect of difluoromethylornithine on the increases in plasma concentrations of reproductive hormones on the afternoon of pro-oestrus in the rat

1989 ◽  
Vol 121 (3) ◽  
pp. 495-499 ◽  
Author(s):  
S. A. Nicholson ◽  
G. A. Wynne-Jones
Keyword(s):  
Differential Effect ◽  
Time Course ◽  
Plasma Concentrations ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Limited Time ◽  
The Times

ABSTRACT In our colony of female rats (220–320 g body weight) undergoing regular 4-day oestrous cycles there were significant, marked rises in concentrations of LH, FSH and prolactin between 09.00 and 19.00 h on pro-oestrus. The i.p. injection of difluoromethylornithine (DFMO; 40–400 mg/kg), a specific inhibitor of the activity of ornithine decarboxylase, at 15.00 h on prooestrus had a differential effect on the rise in plasma concentrations of the various hormones thereafter. The drug produced a significant, partial, dose-related suppression of the rise in plasma concentrations of LH and prolactin, but had no significant effect on the rise in FSH. For time-course studies, 120 mg DFMO/kg were injected at 13.00, 15.00 or 17.00 h and groups of animals killed at 19.00 h. Only the injection at 15.00 h was effective in causing a significant reduction in plasma concentrations of LH and prolactin at 19.00 h. Pituitary content of the hormones was found to be unaffected by the administration of DFMO at the times and doses tested. These results suggest that DFMO has a selective inhibitory effect on enhanced LH and prolactin secretion on the afternoon of pro-oestrus in the rat, whilst not affecting FSH release. There seems to be a limited time (after 13.00 but before 17.00 h) during which its administration is effective. Journal of Endocrinology (1989) 121, 495–499

Alterations in the Golgi Apparatus of the Breast Gland of the Rat During Pregnancy, Lactation, and Involution

1971 ◽  
Vol 29 ◽  
pp. 566-567
Author(s):  
Tariq M. Murad
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Golgi Apparatus ◽  
Rough Surface ◽  
Functional State ◽  
Secretory Activity ◽  
Pregnant Rats ◽  
Pregnancy And Lactation ◽  
Breast Gland

The mammary gland proliferates and differentiates into its functional state under the influence of various hormones secreted during pregnancy and lactation. Lipid, protein, and carbohydrates, which are important constituents of milk, are known to be secreted by this gland. These substances are synthesized and secreted by the mammary gland in varying concentrations during the gestation and lactation periods. The Golgi apparatus is known to play an important role in the secretory activity of the cells. It is the site of the formation of glycoprotein on the rough surface of the endoplasmic reticulum. In a previous study we were able to show the formation of two types of proteins formed in the epithelial cells of the mammary ductules of pregnant rats that were secreted into the lumina before parturition. The Golgi apparatus played no part in the formation of these particles.

A modulatory role of endogenous opioids on prolactin secretion at the end of pregnancy in the rat

1994 ◽  
Vol 140 (1) ◽  
pp. 97-102 ◽  
Author(s):  
M Soaje ◽  
R P Deis
Keyword(s):  
Time Course ◽  
Prolactin Secretion ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Serum Prolactin ◽  
Serum Progesterone ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Ru 486 ◽  
Prolactin Suppression

Abstract It is well known that the fall in serum progesterone concentrations during late pregnancy induces prolactin secretion in rats. On day 19 of pregnancy, administration of 10 mg of the antiprogesterone RU-486/kg induced a small but significant increase in serum prolactin. A lower dose (2 mg/kg) was not effective. Administration of naloxone (2 mg/kg) to pregnant rats on day 19 of pregnancy did not modify circulating prolactin but, after RU-486 treatment, a notable increase in serum prolactin was obtained 30 min after naloxone was given. The lack of effect of naloxone-methobromide in pregnant rats pretreated with RU-486 may indicate that the opioid-induced prolactin suppression acts centrally, most probably at the hypothalamic level. During day 21 of pregnancy, the time-course of prolactin secretion, measured at 0900, 1400, 1900 and 2200 h, was inversely correlated with circulating progesterone levels. At 0900 h, serum prolactin was very low with high serum progesterone concentrations but a significant increase in serum prolactin occurred at 2200 h; this was coincident with a significant decrease in the steroid. The stimulatory effect of naloxone on prolactin secretion was clearly dependent on the circulating progesterone level. Thus, at 1900 h of day 21, naloxone induced a significant increase in serum prolactin but, at 2200 h, the opioid antagonist dramatically enhanced the circulating level of prolactin. The serum prolactin increase induced by naloxone at 1900 h was prevented by the s.c. administration of 5 mg progesterone given 7 h earlier. Similarly, the large increase in serum prolactin levels at 1800 h on day 19 of pregnancy, after administration of RU-486 plus naloxone, was completely abolished by treatment with CB154. The lack of effect of RU-486 and naloxone on serum prolactin levels in virgin rats on the day of pro-oestrus demonstrates that the effect of naloxone on prolactin in pregnant rat is peculiar to the end of pregnancy. In conclusion, the attenuation of the central inhibitory action of progesterone facilitates the release of prolactin which is dramatically enhanced by naloxone treatment. These results provide an important new insight into the existence of a neuromodulatory regulation of prolactin secretion by the opioid system showing a paradoxical opioid-induced prolactin suppression at the end of pregnancy. Journal of Endocrinology (1994) 140, 97–102

Difference in luteal and placental P45017α: substrate preference and hormonal regulation in the rat

1987 ◽  
Vol 115 (3) ◽  
pp. 387-393
Author(s):  
B. Eckstein ◽  
I. Khan ◽  
G. Gibori
Keyword(s):  
Corpus Luteum ◽  
Hormonal Regulation ◽  
Inhibitory Effect ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Substrate Preference ◽  
Corpora Lutea ◽  
Pregnant Rats ◽  
Significant Difference ◽  
Time Point

ABSTRACT The purpose of this study was to assess the substrate specificity of P45017α in both the corpus luteum and placenta of pregnant rats, and to analyse the site at which LH/human chorionic gonadotrophin (hCG) regulates the activities of this enzyme. To distinguish the substrate preference, placentas and corpora lutea were obtained from rats on day 15 of pregnancy. Tissues were homogenized and the 10 000 g supernatants incubated in the presence of equimolar concentrations of [14C]progesterone and [3H]17α-hydroxyprogesterone as substrate with either NADH or NADPH as cofactors for 2, 8, 16 and 24 min. The labelling pattern of both 17α-hydroxyprogesterone and testosterone indicated that the corpus luteum produced testosterone preferentially from progesterone, whereas the placenta principally used 17α-hydroxyprogesterone and synthesized six times as much testosterone from 17α-hydroxyprogesterone than from progesterone. Addition of either NADPH or NADH as cofactors had no effect on substrate preference. The products of the two enzymatic activities were identified by recrystallization to constant 14C/3H ratios. The ratio of 14C/3H in testosterone produced by the corpus luteum was 16-fold higher than in that produced by the placenta. To explore which of the two activities of P45017α is regulated by the gonadotrophin, rats were treated with either 1·5 IU hCG or vehicle between days 13 and 15 of pregnancy. Hydroxylase and lyase activities were determined on day 15 after incubation for 2,8,16 or 24 min in the presence of either NADH or NADPH. Administration of hCG significantly inhibited NADH-dependent 17α-hydroxylase in the placenta at each time-point studied. The inhibition reached 69% at 24 min. Human chorionic gonadotrophin did not affect the NADPH-dependent 17α-hydroxylase and had only a slight inhibitory effect on both NADH- and NADPH-dependent 17,20-lyase activities in the placenta. In contrast to its effect on the placenta, hCG stimulated both NADH- and NADPH-linked 17,20-lyase activities but had no measurable effect on 17α-hydroxylase activities in the corpus luteum. In summary, the results of the present investigation have revealed a significant difference in the behaviour of 17α-hydroxylase/17,20-lyase activities in the placenta and corpus luteum. The substrate preference and the control of both enzyme activities by LH/hCG differs dramatically. J. Endocr. (1987) 115, 387–393

THE EFFECT OF A PLACENTAL MAMMOTROPHIN AND CORTISOL ON THE ULTRASTRUCTURE OF RAT MAMMARY GLAND IN ORGAN CULTURE

1977 ◽  
Vol 86 (3) ◽  
pp. 539-551
Author(s):  
K. D. Njio ◽  
J. M. Peters
Keyword(s):  
Mammary Gland ◽  
Secretory Activity ◽  
Lower State ◽  
Rat Serum ◽  
Pregnant Rats ◽  
Initial Development ◽  
Pregnant Rat ◽  
Rat Mammary Gland ◽  
Secretory Products

ABSTRACT Mammary gland explants obtained from 13 days pregnant rats were cultured for 3, 6 and 9 days in the presence of serum of either virgin rats or 13 days pregnant rats. Insulin was added alone or in combination with cortisol. The way these different forms of treatment affected the ultrastructure was studied. With virgin rat serum plus insulin alone the mammary gland regressed to a lower state of development comparable to that of the virgin rat in vivo. When virgin rat serum was replaced by 13 days pregnant rat serum - which contains rat chorionic mammotrophin - the initial development was maintained, but synthesis of secretory products ceased. When cortisol was added to the virgin rat serum plus insulin, cortisol maintained the differentiated state originally present. Even some secretory activity was induced, but at a minimal level. With cortisol added to the pregnant rat serum plus insulin, the explants were stimulated to synthetize and extrude secretion products.

EFFECTS OF PROGESTERONE AND PROLACTIN ON THE SECRETORY ACTIVITY AND THE NUCLEIC ACID CONTENT OF THE MAMMARY GLAND OF PREGNANT RABBITS

1972 ◽  
Vol 70 (3) ◽  
pp. 603-618 ◽  
Author(s):  
R. Denamur ◽  
C. Delouis
Keyword(s):  
Mammary Gland ◽  
Nucleic Acid ◽  
Essential Role ◽  
Secretory Activity ◽  
Inhibitory Effect ◽  
Nucleic Acid Content ◽  
Mammary Cells ◽  
Milk Secretion ◽  
Qualitative Properties ◽  
Pregnant Rabbit

ABSTRACT Progesterone injected daily at different stages of pregnancy in the rabbit, reduces or temporarily blocks mammary secretion measured on the 24th day either by the incorporation of [14C] glucose into lactose or by the [12C] lactose content of mammary tissues. Progesterone does not affect the number of mammary cells, as determined by the DNA content of the mammary gland, while the quantity of RNA is only reduced if the hormone is injected from the beginning of pregnancy. These results suggest that progesterone has an inhibitory effect on secretory activity, which mainly takes place during the first two thirds of pregnancy. From day 19, twice daily administration of 12.5 IU of prolactin stimulates milk secretion and increases the content of nucleic acids measured on the 24th day. Progesterone (5 mg twice daily) does not prevent these lactogenic effects, nor does it modify the increase in uncleic acids caused by prolactin treatment. Despite the continued presence of progesterone, prolactin has the same qualitative properties in pregnant rabbits deprived of their gonads or pituitary as it has in intact rabbits. Hence prolactin plays an essential role in the mammogenesis and lactogenesis occurring during pregnancy in the rabbit. In addition, our studies show that ovarian secretions other than progesterone are effective under normal conditions of pregnancy, since the administration of progesterone in ovariectomized pregnant rabbit does not allow normal mammary growth despite the maintenance of pregnancy.

Regulation of Msx-1, Msx-2, Bmp-2 and Bmp-4 during foetal and postnatal mammary gland development

Development ◽  
1996 ◽  
Vol 122 (9) ◽  
pp. 2729-2737 ◽  
Author(s):  
D.J. Phippard ◽  
S.J. Weber-Hall ◽  
P.T. Sharpe ◽  
M.S. Naylor ◽  
H. Jayatalake ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Hormonal Regulation ◽  
Time Course ◽  
Mammary Gland Development ◽  
Cancer Cell Line ◽  
Mammary Development ◽  
Gene Products ◽  
Developmentally Regulated ◽  
Gland Development ◽  
Mcf 7

Expression of the Msx-1 and Msx-2 homeobox genes have been shown to be coordinately regulated with the Bmp-2 and Bmp-4 ligands in a variety of developing tissues. Here we report that transcripts from all four genes are developmentally regulated during both foetal and postnatal mammary gland development. The location and time-course of the Bmp and Msx expression point to a role for Msx and Bmp gene products in the control of epithelial-mesenchymal interactions. Expression of Msx-2, but not Msx-1, Bmp-2 or Bmp-4 was decreased following ovariectomy, while expression of the human Msx-2 homologue was regulated by 17beta-oestradiol in the MCF-7 breast cancer cell line. The regulation of Msx-2 expression by oestrogen raises the possibility that hormonal regulation of mammary development is mediated through the control of epithelial-mesenchymal interactions.

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