EFFECTS OF AN ANTISERUM TO LUTEINIZING HORMONE AND STEROID REPLACEMENT THERAPY ON MAINTENANCE OF PREGNANCY IN THE RAT: SERUM AND LUTEAL LEVELS OF PROGESTERONE, TESTOSTERONE AND OESTRADIOL

1981 ◽  
Vol 90 (1) ◽  
pp. 9-18 ◽  
Author(s):  
P. F. TERRANOVA ◽  
G. S. GREENWALD

Pregnant rats were injected s.c. with antiserum to LH (anti-LH) on days 8 or 10 of pregnancy (day 1 = day of sperm-positive vaginal smear) and subsequently given various steroids s.c. to prevent luteolysis and/or abortion. A single injection of 4 mg progesterone on day 8 prevented abortion and luteolysis as shown on day 12 by the presence of fetal swellings and levels of progesterone in serum (88 ±6 (s.e.m.) ng/ml) and corpora lutea (26±3 ng/mg) comparable to control values. After 0·5 ml anti-LH on day 10, a daily dose of 4 mg progesterone prevented abortion in five out of eight animals but by day 13 luteal progesterone was 3·0 ± 0·7 compared with 24±3 ng/mg in controls. After anti-LH on day 8 or 10, daily injections of 1 or 4 mg testosterone propionate or 10 μg, 100 μg or 1 mg oestradiol failed to prevent abortion or to raise luteal concentrations of progesterone to normal values. However, 4 mg testosterone propionate on day 8 or 100 or 500 μg oestradiol on day 10 maintained serum progesterone levels at approximately half those of control values. Treatment with 4 mg testosterone propionate on days 8–11 led to significant increases in serum and luteal levels of testosterone and oestradiol on day 12; on day 10 exogenous oestradiol (100 or 500 μg) increased serum and luteal levels of oestradiol by day 13. These results, especially treatments begun on day 8, are difficult to reconcile with the current concept that the luteotrophic action of LH in the pregnant rat is exerted by increasing luteal androgens that are aromatized to oestrogens which then act as the direct luteotrophic stimulus.

1981 ◽  
Vol 90 (1) ◽  
pp. 19-30 ◽  
Author(s):  
P. F. TERRANOVA ◽  
G. S. GREENWALD

Pregnant rats were injected s.c. at 09.00 h on day 8 of pregnancy (day 1 = sperm-positive vaginal smear) with either 0·2 or 0·5 ml equine antiserum to bovine LH (anti-LH) while control rats were injected with 0·5 ml normal horse serum (NHS). Rats were decapitated 1,3,6, 24 and 48 h later and serum was saved for radioimmunoassay of progesterone, androstenedione, testosterone, oestrone and oestradiol. One ovary was kept for histology, and from the other, corpora lutea (three/animal) and the non-luteal ovary (ovarian remnant from which all corpora lutea were removed) were saved for steroid determinations. The production rate of steroids by the luteal and non-luteal ovarian compartment was assessed by incubation in Krebs–Ringer bicarbonate buffer for 2 h. A significant decrease in the serum concentrations of all steroid hormones was induced by 6 h after treatment with anti-LH; progesterone being the first hormone to be consistently reduced (by 3 h). The steroid concentrations remained lower than those in control rats on days 9 and 10. A single injection of anti-LH reduced the number of healthy antral follicles by 3 h but there were always two to four normal antral follicles per ovary on days 8–10. The initial hormonal changes in the non-luteal ovary after LH deprivation were decreases in the concentration and production rates of the androgens and oestrogens. The initial concentration of non-luteal progesterone was lower 3 and 6 h after anti-LH than in control rats. Although anti-LH induced a decrease in the serum concentration of progesterone 24 and 48 h later, the corpora lutea contained more progesterone on day 8 and produced in vitro more progesterone than controls on day 8 after 0·2 and 0·5 ml anti-LH and on day 9 when only 0·5 ml was given. The increase in the initial concentration of progesterone on day 8 probably represents accumulation resulting from inhibition of luteal progesterone release. It appears, therefore, that the initial alteration after LH deprivation is inhibition of the release of luteal progesterone and this alone is sufficient to account for the interruption of pregnancy. The in-vitro increase in luteal steroidogenesis following LH deprivation was observed to some extent with androstenedione but testosterone was unaffected. Luteal aromatizing enzymes appeared to be very sensitive to LH deprivation on day 8 since the concentration and production of oestrogen decreased without concomitant decreases in androgen. Progesterone (4 mg) administered along with 0·2 ml anti-LH on day 8 prevented luteal regression and the corpora lutea synthesized progesterone and androgens similarly to NHS-treated controls; however, the corpora lutea of the progesterone-treated group contained and produced less oestrogen than controls.


1964 ◽  
Vol 45 (1) ◽  
pp. 1-12 ◽  
Author(s):  
H. E. Swanson ◽  
J. J. van der Werff ten Bosch

ABSTRACT The »early-androgen« syndrome in the rat – i. e. anovulatory ovaries in adult females after a single injection of testosterone propionate (TP) within a week of birth – may not become apparent until some time after the attainment of sexual maturity. Large doses (50 or 100 μg) of TP were effective earlier than lower doses (5 or 10 μg). Rats which received 5 μg TP were ovulating at 10 weeks of age, mated but were infertile at 13 weeks of age, and were anovulatory at 21 weeks. In rats between 10 and 13 weeks old there was a marked fall in the number of corpora lutea in the ovaries of animals which had been given 5 μg TP. Hemi-spaying was followed by compensatory growth of the remaining ovary which consisted of corpora lutea in ovulating, and of follicles in anovulatory rats; little or no compensatory weight increase occurred in animals which seemed to be in the transition stage from the ovulatory to the anovulatory condition.


1975 ◽  
Vol 13 (5) ◽  
pp. 541-545 ◽  
Author(s):  
David J. Elbaum ◽  
Edward M. Bender ◽  
Judith M. Brown ◽  
P. Landis Keyes

1972 ◽  
Vol 53 (1) ◽  
pp. 31-35 ◽  
Author(s):  
K. BROWN-GRANT ◽  
C. S. CORKER ◽  
F. NAFTOLIN

SUMMARY Plasma luteinizing hormone (LH) concentrations were already lower on Day 2 of pregnancy than at the same time after the preceding ovulation in the non-pregnant rat, and fell progressively up to Day 16 of pregnancy. No evidence was obtained of any increase at the time when the ovulatory surge of LH would have occurred if the animal had not become pregnant. Pituitary LH concentration was lower in mated rats on the morning of Day 0 of pregnancy than in unmated controls on the morning of the day of oestrus. Subsequently it increased slowly to reach a level higher than at any stage of the oestrous cycle by Day 8 of pregnancy and remained high until at least Day 16 of pregnancy. Peripheral plasma oestradiol concentration increased late on Day 2 of pregnancy and was still raised on Day 4 but was never more than about one fourth of the peak concentration seen on the morning of prooestrus during the oestrous cycle. There were similar changes in plasma LH and oestradiol concentrations in the 48 h after a single injection of 2·5mg progesterone on the morning of the day of dioestrus, a procedure that delays ovulation by 1 or 2 days. Administration of a synthetic progestational compound (medroxyprogesterone acetate) to pregnant rats delayed blastocyst implantation and the delay was associated with a marked decrease in peripheral plasma LH to levels below those of normal pregnancy.


1973 ◽  
Vol 57 (1) ◽  
pp. 63-74 ◽  
Author(s):  
I. ROTHCHILD ◽  
R. B. BILLIAR ◽  
I. T. KLINE ◽  
G. PEPE

SUMMARY To test the hypothesis of Raj & Moudgal (1970) that luteinizing hormone (LH) is the essential luteotrophin during pregnancy in the rat, pregnant rats were hypophysectomized and hysterectomized on either day 12 or day 15 of pregnancy, and the changes in peripheral serum progesterone level measured. The serum progesterone level remained at approximately the day-12 value for 3 days after hypophysectomy and hysterectomy on day 12, but fell drastically and remained low after the same operation on day 15, or in pseudopregnant rats operated on on day 12, or after removal of the ovaries from pregnant rats on day 12. Oestrogen treatment increased the serum progesterone level slightly in the pregnant rats after hypophysectomy and hysterectomy, but not after ovariectomy; it had no effect in the pseudopregnant rats, with or without deciduomata, or in lactating rats nursing litters of seven to nine pups. The corpora lutea stopped growing or slowly regressed soon after hypophysectomy—hysterectomy in all except the pregnant rats operated on on day 12 and treated with oestrogen, and in these growth was very slight. The luteal content of progesterone did not change for 3 days after hypophysectomy—hysterectomy on day 12 of pregnancy, and fell slightly thereafter. The metabolic clearance rate of progesterone was not significantly changed by hypophysectomy—hysterectomy. It thus appears that true secretion of progesterone continues in pregnant rats for about 3 days after day 12 in the absence of the pituitary and placentas, but at a much lower rate than that found in intact, or in day-12 hypophysectomized pregnant rats (Pepe & Rothchild, 1972a). The placental luteotrophin thus seems to increase the rate of progesterone secretion in the absence of LH. The results do not seem to fit with the hypothesis that LH is essential for progesterone secretion.


Development ◽  
1967 ◽  
Vol 17 (1) ◽  
pp. 171-175
Author(s):  
W. N. Adams Smith ◽  
M. T. Peng

The influence of the testis and of testosterone upon the development of the male genitalia has been extensively investigated and a number of reviews of this work have been published (Jost, 1960; Burns, 1961). However, Witschi (1957) has stressed the need to distinguish between adult sex hormones, such as testosterone, and the secretions of the immature gonad. The formation of corpora lutea in the ovaries transplanted to adult male rats which had been castrated at birth, and the absence of corpus luteum formation in ovaries transplanted to male hosts bearing transplanted testes in the neck from birth, was reported by Pfeiffer in 1936. Similar observations have been reported by Yazaki (1960) and Harris (1964). A single injection of testosterone propionate has been found to lead to permanent sterility and a loss of corpus luteum formation in the ovaries of mice (Barraclough & Leathern, 1954) and rats (Barraclough, 1961).


1960 ◽  
Vol XXXIV (IV) ◽  
pp. 536-542 ◽  
Author(s):  
Richard A. Edgren ◽  
Helene D. Neer

ABSTRACT In an earlier paper simultaneous testosterone propionate (TP) was shown to inhibit the vaginal smear effects of oestrone given over two days to spayed female mice. Deoxycorticosterone acetate (DCA) and progesterone were inactive in that test. Oestrone was given at a dose of 2 μg and the other steroid at 1000 μg. If these same doses were given over a four day period, however, all three steroids blocked the oestrone-induced changes. In a series of tests in which the oestrone was given over four days and the blocker either in one or two day periods, TP was found to antagonize when administered with the early but not with the late oestrone injections. DCA was an inhibitor only when given with the late oestrone administrations. The period of progesterone activity was midway between that for TP and that for DCA, and overlapped each. These patterns of response were best discriminated when the blocker was administered in a single injection.


1976 ◽  
Vol 83 (3) ◽  
pp. 640-650 ◽  
Author(s):  
J. M. Peters ◽  
J. van Marie

ABSTRACT Serum mammotrophic activity was assayed using an organ culture technique with histological endpoints. Using sera of 13 days pregnant rats with 1 to 18 conceptuses, activity was detectable even in the presence of 1 conceptus, but the activity with 1–4 conceptus(es) tended to be less than with 6–18. Serum of rats with 1–3 conceptus(es) was approximately 2–4 times less active than serum of rats with 14 conceptuses. Removal of the conceptuses on day 15 caused loss of mammotrophic activity of the serum, tested 4 days later. When the foetuses, the ovaries or both the foetuses and ovaries were removed on day 15 of pregnancy, mammotrophic activity was present in the serum collected 4 days later. Differences in activity between the treated groups were small. The mammotrophic activity was comparable to the activity of serum of untreated 15 days pregnant rats or 19 days sham-operated pregnant rats. Explanted single fragments of a 19 days pregnant rat placenta released activity into the medium. The placenta retained this capacity even when the foetus had been removed 4 days previously.


1978 ◽  
Vol 78 (1) ◽  
pp. 31-38 ◽  
Author(s):  
G. VANDOREN ◽  
H. VAN BAELEN ◽  
G. VERHOEVEN ◽  
P. DE MOOR

Evidence is presented that the level of α2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats α2u-globulin cannot be detected. Moreover, α2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of α2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of α2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of α2u-globulin.


1994 ◽  
Vol 140 (1) ◽  
pp. 97-102 ◽  
Author(s):  
M Soaje ◽  
R P Deis

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


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