MODIFICATION BY OESTROGENS OF THE REACTION OF THE RAT'S MAMMARY GLAND TO ANDROGENS

1962 ◽  
Vol 41 (1) ◽  
pp. 88-100 ◽  
Author(s):  
Dora Jacobsohn
Keyword(s):  
Growth Hormone ◽  
Mammary Gland ◽  
Present Finding ◽  
Mammary Glands ◽  
List Type ◽  
Simultaneous Treatment ◽  
Alveolar Development ◽  
Hypophysectomized Rats ◽  
Combined Actions

ABSTRACT The investigation is concerned with the question, whether the mammary gland of the rat reacts with alveolar growth to androgens alone or to the combined actions of androgens and oestrogens. Since it is difficult to deprive a rat of oestrogens, the study was performed under conditions in which the gland itself either does or does not react to oestrogens. The results were as follows: Experiments on hypophysectomized rats treated with insulin and cortisone. – This treatment makes the glands responsive to oestrogens. Administration of oestrogens resulted in alveolar development in response to endogenously produced androgens (males injected with PMS) as well as to testosterone injections (gonadectomized rats). Experiments on hypophysectomized rats. – The glands do not react to oestrogens. – Injections of oestrogens together with PMS or testosterone resulted in the abnormal reaction known to occur in the mammary glands of hypophysectomized rats given androgens alone. Alveoli were absent. Confirming previous results with testosterone, the mammary glands of hypophysectomized males injected with PMS reacted abnormally and the reaction was not normalized by simultaneous treatment of the hypophysectomized rats with insulin and cortisone. The hitherto confusing results obtained by other workers who studied the effects of growth hormone and prolactin on the mammary glands of hypophysectomized rats are discussed, in view of the present finding that a response of the rat's mammary gland to oestrogens is a prerequisite for the production of alveolar lobule development by androgens.

INTERACTIONS OF OESTROGENS AND ANDROGENS ON THE MAMMARY GLAND AND GROWTH OF OTHER TISSUES IN HYPOPHYSECTOMIZED RATS TREATED WITH INSULIN, CORTISONE AND THYROXINE

1962 ◽  
Vol 41 (2) ◽  
pp. 287-300 ◽  
Author(s):  
Dora Jacobsohn
Keyword(s):  
Mammary Gland ◽  
Mammary Glands ◽  
The Body ◽  
List Type ◽  
Simultaneous Treatment ◽  
Abnormal Response ◽  
Hypophysectomized Rats ◽  
Different Doses

ABSTRACT In a previous study it was found that oestrogens are necessary for androgens to elicit a development of alveolar lobules in the mammary glands of rats. Since androgens and oestrogens exert synergistic as well as antagonistic actions on mammary glands of e. g. rabbits, the significance of oestrogens in the response of the mammary gland to androgens was further investigated in the rat. The experiments were designed according to the same principles as previously, that is, the response of the gland itself to oestrogens was modified. This was achieved by treatment of hypophysectomized rats with a) thyroxine (negligible response) and b) thyroxine, cortisone and insulin (marked response). The effect of endogenous androgens was studied in males injected with PMS with or without oestrogens. Gonadectomized rats were injected with testosterone and oestrogens. No oestrogens given: The mammary glands of hypophysectomized males injected with PMS showed an abnormal response, irrespective of simultaneous treatment with thyroxine, cortisone and insulin in various combinations. The result confirms previous work with testosterone. Negligible response of the mammary glands to oestrogens: In hypophysectomized rats treated with thyroxine, oestrogens and PMS or testosterone, the response of the glands was uniform and abnormal. The absence of end buds indicated that the response to oestrogens, if present at all, was suppressed by the androgens. Marked response of the mammary glands to oestrogens: In hypophysectomized rats treated with thyroxine, cortisone and insulin another response of the glands to androgens and oestrogens was found. Besides abnormal structures, alveolar lobules were present. The changes produced with different doses of testosterone and oestrone indicated a complicated interplay of the two hormones. Confirming previous observations, records of the length and weight of the body and of the weight of the liver and heart revealed marked growth in the hypophysectomized rats treated with thyroxine, cortisone and insulin.

THE SECRETORY CAPACITY OF THE AUTOTRANSPLANTED HYPOPHYSIS AS INDICATED BY THE EFFECTS OF STEROID HORMONES ON THE MAMMARY GLANDS

1961 ◽  
Vol 38 (3) ◽  
pp. 449-468 ◽  
Author(s):  
Kurt Ahrén
Keyword(s):  
Growth Hormone ◽  
Mammary Gland ◽  
Pituitary Gland ◽  
Mammary Gland Development ◽  
Mammary Glands ◽  
Male Rats ◽  
Alveolar Development ◽  
Hypophysectomized Rats ◽  
Gland Development ◽  
Secretory Capacity

ABSTRACT In the present experiments the secretory capacity of the pituitary gland, autotransplanted to the kidney capsule, was studied with special regard to the secretion of prolactin and growth hormone, using the response of the mammary glands to oestrone (3-hydroxy-oestra-1,3,5(10)-trien-17-one) and progesterone (pregn-4-ene-3,20-dione) in castrated female and male rats as indicator. The main results were as follows: 1) Daily injections of 10 μg of oestrone + 4 mg of progesterone stimulated slight duct growth and marked but not maximal lobule-alveolar development in the mammary glands of rats with transplanted hypophysis. In rats with intact pituitary gland this treatment produced more extensive duct growth and more marked alveolar development. 2) Daily injections of 1 μg of oestrone did not stimulate mammary gland development in rats with transplanted pituitary gland. The same treatment produced slight but definite duct growth in rats with intact pituitary gland. 3) Daily injections of 10 μg of oestrone stimulated slight duct growth and restricted lobule-alveolar development in rats with transplanted hypophysis. In rats with intact pituitary gland this treatment produced more extensive growth of the duct system. 4) In hypophysectomized rats all dose levels of oestrone and progesterone were ineffective in promoting mammary gland development. Combined with prolactin these hormones stimulated, in hypophysectomized rats, a mammary gland development which, qualitatively as well as quantitatively, was very similar to that found in rats with transplanted pituitary gland. These results indicate that the transplanted pituitary gland secreted considerable amounts of prolactin but did not secrete growth hormone or secreted it in only very small amounts.

INFLUENCE OF THE ADRENAL CORTEX ON GROWTH PROCESSES IN THE RAT MAMMARY GLAND

1964 ◽  
Vol 30 (2) ◽  
pp. 171-179 ◽  
Author(s):  
L. HAMBERGER ◽  
K. AHRÉN
Keyword(s):  
Mammary Gland ◽  
Mammary Glands ◽  
Sprague Dawley ◽  
Growth Processes ◽  
Alveolar Development ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
Rat Mammary Gland ◽  
Adrenalectomized Rats

SUMMARY The role of adrenal cortical hormones in the response of the rat mammary gland to testosterone was studied in Sprague-Dawley rats. In gonadectomized rats with intact adrenals, local percutaneous application of testosterone stimulated lobulo-alveolar development in the mammary glands. This effect of testosterone was markedly reduced after adrenalectomy. Injections of cortisone into the adrenalectomized rats restored the mammary gland response to testosterone, whereas injections of oestrone did not. In adrenalectomized and hypophysectomized rats, injections of testosterone in combination with growth hormone produced a marked alveolar development in the mammary glands. The importance of gonadal, hypophysial and adrenocortical hormones for various growth processes in the mammary glands is discussed.

THE SECRETORY CAPACITY OF THE AUTOTRANSPLANTED HYPOPHYSIS AS INDICATED BY THE EFFECTS OF STEROID HORMONES ON THE MAMMARY GLANDS

1962 ◽  
Vol 39 (3) ◽  
pp. 338-354 ◽  
Author(s):  
Kurt Ahrén
Keyword(s):  
Growth Hormone ◽  
Mammary Gland ◽  
Pituitary Gland ◽  
Steroid Hormones ◽  
Testosterone Propionate ◽  
Mammary Glands ◽  
Kidney Capsule ◽  
Alveolar Development ◽  
Rat Mammary Gland ◽  
Secretory Capacity

ABSTRACT The capacity of the rat mammary gland to respond to testosterone stimulation with lobule-alveolar development only when growth hormone is present, has in these experiments been used as a method for studying whether the pituitary gland, autotransplanted into the kidney capsule, can secrete growth hormone. Injections of 0.05 or 0.25 mg of testosterone propionate daily for 14 days did not stimulate any lobule-alveolar development in the mammary glands of castrated rats with autotransplanted hypophysis. When this treatment was given for about 4 weeks, a few alveoli were seen in the mammary glands. In castrated rats with intact pituitary gland the same doses of testosterone propionate stimulated an extense lobule-alveolar development even after only 14 days of treatment. Injections of testosterone propionate together with growth hormone in rats with autotransplanted hypophysis stimulated the same degree of lobule-alveolar development as did injections of testosterone alone in rats with intact pituitary gland. These observations on the mammary glands indicate that there is a considerable deficiency of growth hormone in rats with the pituitary gland autotransplanted into the kidney capsule. These results are discussed, together with the value of the method used for estimating the presence of growth hormone.

INTERACTIONS OF OESTRONE AND TESTOSTERONE ON MAMMARY GLANDS OF MALE RABBITS

1961 ◽  
Vol 36 (1) ◽  
pp. 141-156 ◽  
Author(s):  
B. Bengtsson ◽  
A. Norgren
Keyword(s):  
Mammary Gland ◽  
Testosterone Propionate ◽  
Mammary Glands ◽  
List Type ◽  
Stunted Growth ◽  
Abnormal Growth ◽  
Growth Reaction ◽  
Extensive Growth ◽  
Higher Doses

ABSTRACT The effect of testosterone and oestrone on the mammary glands of castrated male rabbits was studied. Testosterone propionate was used in daily doses from 0.5 to 80 mg. The doses of oestrone ranged from 0.05 to 25 μg per day. Mammary glands were examined after 14, 28 or 56 days of injections. 1) Testosterone in doses below 20 mg failed to affect the mammary glands. With 40 or 80 mg a distinct, though abnormal growth reaction was consistently obtained. 2) Oestrone in doses lower than 0.5 μg did not stimulate mammary growth. With 0.5 μg and higher doses extensive growth of the mammary glands occurred. Stunted growth and secretion were found in the mammary glands of rabbits injected with 12.5 or 25 μg oestrone. 3) Testosterone in doses of 1 or 5 to 10 mg depressed or abolished the response of the mammary glands to 0.5 μg oestrone. When testosterone, in doses ineffective when given alone, was added to at least 3.125 μg oestrone, the mammary glands developed alveoli. The abnormalities produced by the highest doses of oestrone studied were exaggerated by the addition of testosterone. 4) The observations indicate a complicated interplay between the actions of testosterone and oestrone on the mammary gland of the rabbit. The interactions between testosterone and oestrone are presumably different from those observed between progesterone and oestrone.

Differential expression of the growth hormone receptor and growth hormone-binding protein in epithelia and stroma of the mouse mammary gland at various physiological stages

1999 ◽  
Vol 161 (1) ◽  
pp. 77-87 ◽  
Author(s):  
YN Ilkbahar ◽  
G Thordarson ◽  
IG Camarillo ◽  
F Talamantes
Keyword(s):  
Growth Hormone ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Growth Hormone Receptor ◽  
Mammary Epithelial Cells ◽  
Late Pregnancy ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Mrna Levels

Increasing evidence suggests that GH is important in normal mammary gland development. To investigate this further, we studied the distribution and levels of growth hormone receptor (GHR) and GH-binding protein (GHBP) in the mouse mammary gland. At three weeks of age, the epithelial component of the right fourth inguinal mammary gland of female mice was removed. These animals were then either maintained as virgins until they were killed or they were mated. One group of the mated mice was killed on day 18 of pregnancy and the remaining mated animals were allowed to carry their pups until term and were killed on day 6 of lactation. At the time of death, both the intact left and the de-epithelialized right mammary glands were collected from all three groups. Some of the intact glands served as a source of epithelial cells, free of stroma. The mRNA levels for GHR and GHBP were measured in intact glands, epithelia-cleared fat pads, and isolated mammary epithelial cells. GHR and GHBP mRNAs were expressed in both the mammary epithelium and stroma. However, the levels of both GHR and GHBP mRNAs were significantly higher in the stroma as compared with the epithelium component. This increase for both mRNAs was from 3- to 12-fold at each physiological state examined. In the intact gland, both GHR and GHBP transcripts were highest in virgins, declined during late pregnancy, and the lowest levels were found in the lactating gland. GHBP and GHR protein concentrations were also assessed in intact glands and epithelia-free fat pads. Similar to the mRNAs, GHR and GHBP protein levels (means+/-s.e.m.) in intact glands were highest in virgin mice (0.891+/-0.15 pmoles/mg protein and 0.136+/-0.26 pmoles/mg protein respectively), declined during late pregnancy (0. 354+/-0.111 pmoles/mg protein and 0.178+/-0.039 pmoles/mg protein respectively), and were lowest during lactation (0.096+0.037 pmoles/mg protein and 0.017+0.006 pmoles/mg protein respectively). Immunocytochemistry utilizing specific antisera against mouse (m) GHR and mGHBP revealed that the two proteins are localized to both the stroma and parenchyma of mouse mammary glands, with similar patterns of immunostaining throughout the different physiological stages analyzed. GHR immunolocalized to the plasma membrane and cytosol of mammary epithelial cells and adipocytes, whereas the GHBP immunostaining was nuclear and cytosolic. In conclusion, we report here that GHR and GHBP mRNAs and proteins are expressed in both the epithelium and the stroma of mammary glands of virgin, pregnant, and lactating mice. In intact glands, GHR and GHBP proteins, as well as their transcripts are higher in abundance in virgin relative to lactating mice. At all physiological stages, GHR and GHBP mRNA levels are higher in the stroma compared with the parenchyma. These findings indicate that the actions of GH in the mammary gland are both direct through its binding to the epithelia, and indirect by binding to the stroma and stimulation of IGF-I production which, in turn, affects mammary epithelial development.

INTERACTION BETWEEN PROLACTIN AND THYROXINE IN MOUSE MAMMARY GLAND LOBULO-ALVEOLAR DEVELOPMENT IN VITRO

1969 ◽  
Vol 45 (4) ◽  
pp. 579-583 ◽  
Author(s):  
D. V. SINGH ◽  
H. A. BERN
Keyword(s):  
Mammary Gland ◽  
Synergistic Effects ◽  
Synthetic Medium ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Intact Female ◽  
Antagonistic Effects ◽  
Alveolar Development ◽  
Development In Vitro

SUMMARY Intact female BALB/cCrgl mice, 3–4 weeks old, were pretreated with oestrogen and progesterone for 9 days. Whole mammary glands from these mice were cultivated for 5 days in a synthetic medium supplemented with aldosterone (A), prolactin (MH) and insulin (I), with and without thyroxine (T4) at concentrations ranging from 0·01 to 5 μg./ml. A medium containing 1 μg. A +5 μg.MH +5 μg.I/ml. was generally optimal for lobulo-alveolar development. Addition of thyroxine to this combination resulted in a decrease in development which was highly significant at higher concentrations. However, when cultures were maintained in media containing suboptimal or low amounts of prolactin (1 μg. A + 3 μg. MH +5 μg. I/ml. and 1 μg. A + 1 μg. MH +5 μg. I/ml., respectively), the results indicate two possible effects of thyroxine: lower amounts of thyroxine had synergistic effects, whereas greater amounts had antagonistic effects on lobulo-alveolar development.

scholarly journals Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4547-4557 ◽  
Author(s):  
Elizabeth Tonner ◽  
Michael C. Barber ◽  
Gordon J. Allan ◽  
James Beattie ◽  
John Webster ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Death ◽  
Mammary Gland ◽  
Transgenic Mice ◽  
Dna Content ◽  
Caspase 3 ◽  
Transgenic Animals ◽  
Mammary Glands ◽  
Mammary Development ◽  
Igf I

We have previously demonstrated that IGFBP-5 production by mammary epithelial cells increases dramatically during involution of the mammary gland. To demonstrate a causal relationship between IGFBP-5 and cell death we created transgenic mice expressing IGFBP-5 in the mammary gland using a mammary-specific promoter, β-lactoglobulin. DNA content in the mammary glands of transgenic mice was decreased as early as day 10 of pregnancy. Histological analysis indicated reduced numbers of alveolar end buds, with decreased ductal branching. Transgenic dams produced IGFBP-5 in their milk at concentrations similar to those achieved at the end of normal lactation. Mammary cell number and milk synthesis were both decreased by approximately 50% during the first 10 days of lactation. BrdU labelling was decreased, whereas DNA ladders were increased in transgenic animals on day 1 of lactation. On day 2 postpartum, the epithelial invasion of the mammary fat pad was clearly impaired in transgenic animals. The concentrations of the pro-apoptotic molecule caspase-3 and of plasmin were both increased in transgenic animals whilst the concentrations of 2 prosurvival molecules Bcl-2 and Bcl-xLwere both decreased. In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I we examined IGF receptor phosphorylation and Akt phosphorylation and showed that both were inhibited. We attempted to “rescue” the transgenic phenotype by using growth hormone to increase endogenous IGF-I concentrations or by implanting minipumps delivering an IGF-1 analogue, R3-IGF-1, which binds weakly to IGFBP-5. Growth hormone treatment failed to affect mammary development suggesting that increased concentrations of endogenous IGF-1 are insufficient to overcome the high concentrations of IGFBP-5 produced by these transgenic animals. In contrast mammary development (gland weight and DNA content) was normalised by R3-IGF-I although milk production was only partially restored. This is the first demonstration that over-expression of IGFBP-5 can lead to; impaired mammary development, increased expression of the pro-apoptotic molecule caspase-3, increased plasmin generation and decreased expression of pro-survival molecules of the Bcl-2 family. It clearly demonstrates that IGF-I is an important developmental/survival factor for the mammary gland and, furthermore, this cell death programme may be utilised in a wide variety of tissues.

scholarly journals Local Insulin-Like Growth Factor-II Mediates Prolactin-Induced Mammary Gland Development

2003 ◽  
Vol 17 (3) ◽  
pp. 460-471 ◽  
Author(s):  
Russell C. Hovey ◽  
Jessica Harris ◽  
Darryl L. Hadsell ◽  
Adrian V. Lee ◽  
Christopher J. Ormandy ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Early Pregnancy ◽  
Insulin Receptors ◽  
Mammary Glands ◽  
Mouse Mammary Gland ◽  
Mammary Epithelial ◽  
Receptor Expression ◽  
Mammary Tissue ◽  
Alveolar Development

Abstract Prolactin (PRL) is a major determinant of mammary epithelial cell proliferation during alveolar development in sexually mature and pregnant mice. To date, it has not been clear whether PRL effects these responses alone or by also invoking the action of autocrine/paracrine growth factors. In this study, we provide evidence that part of the effect of PRL on mammary gland growth is mediated by IGF-II. During sexual maturity and in early pregnancy, the level of IGF-II mRNA in the mammary gland was increased concurrent with increased PRL receptor expression. The level of IGF-II mRNA was reduced in mammary tissue from PRL receptor−/− mice during early pregnancy, and explants of mouse mammary gland and HC11 mammary epithelial cells both increased their expression of IGF-II after exposure to PRL in vitro. These findings coincided with the demonstration that IGF-II stimulated alveolar development in mammary glands in whole organ culture. PRL was most efficacious in stimulating IGF-II gene transcription from promoter 3 of the mouse IGF-II gene in vitro. Insight into the mechanism by which PRL induced IGF-II expression was provided by the fact that it was blocked by the Jak2 inhibitor AG490 and the MAPK inhibitor PD98059. Finally, induction of insulin receptor substrate (IRS)-1 in the mammary glands of PRL-treated mice and induction of IRS-1 and IRS-2 after treatment with PRL plus progesterone indicates that these molecules are induced by PRL as potential signaling intermediates downstream from IGF-I/insulin receptors. Together, these data demonstrate a role for IGF-II as a mediator of PRL action in the mouse mammary gland during ductal branching and alveolar development.

EFFECTS OF THYROXINE ON GROWTH OF MAMMARY GLANDS, WHOLE BODY, HEART AND LIVER IN HYPOPHYSECTOMIZED RATS TREATED WITH INSULIN, CORTISONE AND OVARIAN STEROIDS

1960 ◽  
Vol XXXV (I) ◽  
pp. 107-134 ◽  
Author(s):  
Dora Jacobsohn
Keyword(s):  
Mammary Glands ◽  
The Body ◽  
Whole Body ◽  
Prolonged Treatment ◽  
List Type ◽  
Ovarian Steroids ◽  
Heart Ventricles ◽  
General Metabolism ◽  
Hypophysectomized Rats ◽  
Long Acting

ABSTRACT The effect of thyroxine on the growth of mammary glands and other tissues was studied in rats devoid of hypophysial hormones. 1. Experimental procedures permitting prolonged treatment of hypophysectomized rats with thyroxine together with long acting insulin, cortisone, oestradiolbenzoate and progesterone in doses inducing growth were worked out. It was found essential 1) to subject the rats to a fortnight's pretreatment with thyroxine before superimposing the other hormones and 2) to avoid cortisone in doses larger than 0.25 mg daily. 2. Administration of thyroxine with or without cortisone to gonadectomized hypophysectomized rats injected with oestradiolbenzoate and progesterone resulted in a development of end buds whilst other mammary tissues remained atrophic. 3. Thyroxine enhanced the growth reaction of the mammary glands to oestradiolbenzoate and progesterone in gonadectomized hypophysectomized rats treated with insulin and cortisone. 4. Determinations of the weight and length of the body and of the weight of the liver, heart ventricles and adrenal glands showed that thyroxine in the hypophysectomized rats treated with insulin, cortisone and ovarian steroids enhanced the growth of the body and heart ventricles. 5. The observations made in the present work support the view that the growth of the mammary gland is dependent upon the state of the general metabolism.

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