Effects of long-term administration of high doses of medroxyprogesterone acetate on hormone receptors and target organs in the female rat

1984 ◽  
Vol 103 (3) ◽  
pp. 287-293 ◽  
Author(s):  
F. Di Carlo ◽  
S. Racca ◽  
G. Conti ◽  
E. Gallo ◽  
G. Muccioli ◽  
...  

ABSTRACT The changes in oestrogen, progesterone and prolactin receptor levels in target organs, and the macroscopic and microscopic modifications of uterus, ovary, adrenal and pituitary gland induced by long-term administration of high doses of medroxyprogesterone acetate (MPA) were investigated in female rats. Medroxyprogesterone acetate was injected i.m. for 30 days at daily doses of 7·5, 15 and 75 mg/kg. Oestrogen and/or progesterone-binding capacities were remarkably reduced at all doses of MPA used both in the uterus and pituitary gland. Furthermore, MPA caused a very evident reduction in the weight of pituitary glands, ovaries, adrenals and uterus. In all MPA-treated rats corpora lutea were absent from the ovaries, whereas the adrenals showed a significant reduction in the thickness of the cortex. In accordance with this, there was no evidence of ACTH-producing cells in the pituitary glands. Prolactin-producing cells were also absent, while GH-producing cells were present. Serum prolactin levels were significantly reduced at all doses of MPA used. A dramatic reduction of prolactin receptor concentrations was observed in the liver and the ovaries of MPA-treated rats. The results suggest that MPA acts as an antioestrogenic drug both by reducing the number of oestrogen receptors in target tissues and by changing the structure (and perhaps the function) of those organs (pituitary glands, ovaries and adrenals) which are, directly or indirectly, a source of oestrogens. The decreased synthesis of prolactin and the reduction of the number of prolactin receptors (which, on the contrary, are both increased by oestrogens) might be considered as additional antioestrogenic effects of MPA. J. Endocr. (1984) 103, 287–293

1972 ◽  
Vol 50 (8) ◽  
pp. 768-773 ◽  
Author(s):  
E. A. Ibrahim ◽  
B. E. Howland

The concentration of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in serum and pituitary glands was studied in intact female rats and rats that were ovariectomized on day 0 of the experiment and then starved or fed for 2, 4, 7, or 9 days. Ovariectomy resulted in enhanced rates of synthesis and release of FSH and LH as indicated by the significant (P < 0.01) rises in the concentration of both hormones in the pituitary gland and serum.Starvation resulted in a decrease in body and pituitary weight. The concentration of FSH and LH in pituitary glands of starved rats was higher (P < 0.05) than that in fed rats on days 7 and 9. The concentration of FSH and LH in serum of starved rats was increased after ovariectomy but the levels on days 7 and 9 were lower than those of fed rats.These results suggest that the synthesis of FSH and LH was enhanced in both starved and fed rats following ovariectomy while the rate of release of both hormones was decreased at 7 and 9 days of starvation in comparison with rats fed ad libitum.


Biologia ◽  
2013 ◽  
Vol 68 (4) ◽  
Author(s):  
Peter Orendáš ◽  
Ivan Ahlers ◽  
Bianka Bojková ◽  
Monika Kassayová ◽  
Peter Kubatka ◽  
...  

AbstractChemopreventive effect of non-steroidal antiinflammatory drugs (NSAIDs) in mammary carcinogenesis was reported in several studies. In this study, the effect of a nonselective cyclooxygenase inhibitor diclofenac (DICLO) in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats was evaluated. NMU was administered to animals intraperitoneally in two doses of 50 mg kg−1 b.w. within postnatal days 42-48. In experiment A (short-term administration), DICLO was administrated intramuscularly (5 mg kg−1 b.w.) every other day, starting 3 days before and for subsequent 25 days after first NMU injection. In experiment B (long-term administration), DICLO was administered in tap water (0.01 mg ml−1) continually, starting 7 days before and for subsequent 22 weeks after first NMU dose. The study was terminated 22 weeks after the first dose of NMU in both experiments. After DICLO treatment, tumor frequency per group was reduced in both variants of drug administration: in experiment A by 38% and in experiment B by 39.5%. Moreover, DICLO decreased tumor incidence by 11.5% and delayed tumor latency by 14 days in experiment B. In our preventive-curative experiments DICLO decreased some parameters of NMU-induced rat mammary carcinogenesis, mainly the tumor frequency.


1970 ◽  
Vol 48 (2) ◽  
pp. 85-89 ◽  
Author(s):  
Robert L. Hazelwood ◽  
John G. Galaznik

Acetone-dried pituitary glands from young adult female rats (starting weight 165–168 g) previously injected (s.c.) with doses of insulin of 0.5 U to 1.0 U/kg body weight for 4 days, and then with 2.0 U/kg 6 days a week for an additional 34 days, were bioassayed in young hypophysectomized rats for growth hormone content. Insulin-injected rats gained significantly more weight than saline-injected controls. The tibia cartilage width of the insulin-injected donor rats was greater than that of control rats after 9, 17, 24, and 31 days of insulin; pituitary gland preparations from these insulin-injected rats increased tibia cartilage widths slightly but significantly over those of rats injected with control pituitary gland preparations.


Author(s):  
P. W. Coates ◽  
C. A. Blake ◽  
D. S. Maxwell ◽  
C. H. Sawyer

In rats, physiological studies show that ovariectomy results in a reduced concentration of circulating prolactin. Conversely, ovariectomized rats given estrogen have elevated serum prolactin and increased amounts of prolactin in the anterior pituitary gland. Separate electron microscopic studies suggest modifications in fine structure of prolactin producing (LTH) cells based on relatively large cumulative amounts of estrogen given alone or with comparably high doses of progesterone to adult virgin female or ovariectomized rats. This study was undertaken to provide a correlated morphological and physiological investigation of LTH cells and prolactin levels in a model commonly used by many researchers.Six to seven weeks after bilateral ovariectomy, a group of adult female rats was primed by a subcutaneous injection of 50 ng of estradiol benzoate and 25 mg of progesterone.


1980 ◽  
Vol 87 (3) ◽  
pp. 383-392 ◽  
Author(s):  
E. Y. ADASHI ◽  
A. J. W. HSUEH ◽  
S. S. C. YEN

Alterations in the concentrations of oestrogen receptors in the uterus, pituitary gland and hypothalamus during the 2 weeks following a single administration of clomiphene citrate (Clomid) to immature, bilaterally ovariectomized rats were investigated. Examination of the uterine wet weight at 1, 7 and 14 days following a single injection of Clomid (100 μg, 250 μg or 10 mg) indicated significant time- and dose-related increments from a control value of 45 ± 2 (s.e.m.) mg to a maximum of 123 ± 3 mg (250 μg dose at 14 days). In contrast, a single injection of oestradiol led to a transient increase in the uterine weight on day 1 to 94 ± 6 mg, but was without effect by days 7 and 14. Analysis of the uterine DNA content 7 and 14 days after treatment with Clomid revealed significant increments from control values of 390 ± 10 μg to a high level of 558 ± 8 μg (10 mg dose at 7 days). There was a transient retention of nuclear oestrogen receptors and rapid replenishment of cytoplasmic oestrogen receptors in less than 24 h in the uteri of animals treated with oestradiol (25 μg), but determinations of receptor content in Clomid-treated animals revealed prolonged retention of nuclear receptors and delayed replenishment of cytoplasmic receptors. The duration and extent of retention of nuclear receptors and depletion of cytoplasmic receptors after treatment with Clomid were found to be dose-dependent. Fourteen days after Clomid treatment, levels of oestrogen receptors in nuclei from the uterus were still raised in all treatment groups, whereas replenishment of cytoplasmic receptors was complete in animals treated with the lower doses (100 and 250 μg) of Clomid. A single injection of Clomid (250 μg) induced similar prolonged retention of nuclear receptors and delayed depletion of cytoplasmic receptors in pituitary tissue. In contrast, changes in the content of oestrogen receptors in the hypothalamus following Clomid treatment were minimal. The limited effect of Clomid on hypothalamic tissue may mean that the pituitary gland is a more important target for this compound than is the hypothalamus. The findings have confirmed earlier reports on the long-term uterotrophic effect of Clomid and have suggested that under these long-term, in-vivo conditions, Clomid acts in the uterus and pituitary gland as a long-acting oestrogen characterized by prolonged retention of oestrogen receptors in the nucleus and delayed, but otherwise effective, replenishment of the oestrogen receptors in the cytoplasm.


1990 ◽  
Vol 124 (3) ◽  
pp. 381-386 ◽  
Author(s):  
M. J. Gardner ◽  
D. J. Flint

ABSTRACT Treatment of neonatal rats on days 2–5 with antibodies against rat GH (rGH) markedly reduced body weight gain and serum concentrations of insulin-like growth factor-I for 6–8 weeks in both females and males, after which weight gain normalized without evidence of catch-up growth. There were no significant effects on serum prolactin, tri-iodothyronine or corticosterone. Testis and ovarian weights were reduced, although only in proportion to body size. In females, but not males, the treated rats, though lighter, had increased fat deposition in the parametrial depot. Pituitary weight was considerably reduced over 100 days later, as was the pituitary content of GH, but not prolactin. The response to GH-releasing factor of both male and female rats was also greatly reduced at this time. Taken together with the fact that these rGH antibodies can bind directly to somatotrophs, we propose that the long-term effects of the antibodies are induced by specific somatotroph destruction. Journal of Endocrinology (1990) 124, 381–386


2015 ◽  
Vol 3 (8) ◽  
pp. 1197-1207 ◽  
Author(s):  
Sujit Kootala ◽  
Dmitri Ossipov ◽  
Jeroen JJP van den Beucken ◽  
Sander Leeuwenburgh ◽  
Jöns Hilborn

Bisphosphonate-functionalized hyaluronic can potentially reduce long-term administration of high doses of BPs.


1999 ◽  
Vol 45 (5) ◽  
pp. 553-565 ◽  
Author(s):  
P. Isaac RABBANI ◽  
Nasreen M. SHEIKH ◽  
Stuart J. CHIRTEL ◽  
Randolph JACKSON ◽  
George RUFFIN

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