Hormone concentrations and ovulatory response in rats treated with antiprogestagens

1991 ◽  
Vol 129 (3) ◽  
pp. 423-429 ◽  
Author(s):  
J. Th. J. Uilenbroek

ABSTRACT Administration of antiprogestagens (2 mg/day) to female rats for 21 days induces high serum prolactin levels. These levels stimulate luteal progesterone production and an increase in ovarian weight. Compared with RU486 (mifepristone) the increase in prolactin is less after treatment with ZK299 (onapristone), an antiprogestagen with lower antiglucocorticoid activity. To study whether cyclic ovulations occur in rats treated with antiprogestagens, 5-day cyclic rats were given daily injections of RU486 or ZK299 (2 mg) from metoestrus (day 1) to pro-oestrus. This treatment advanced the forthcoming ovulation by 1 day; however, the ovulation rate was low. Injection of 10 IU human chorionic gonadotrophin on the afternoon of pro-oestrus (day 3) increased the ovulation rate, but not to the level found in oil-treated rats. Serum LH concentrations measured from metoestrus to oestrus at 10.00 and 17.00 h were higher in antiprogestagen- than in oil-treated rats from day 2 (17.00 h) onwards. A low preovulatory LH surge was found in antiprogestagen-treated rats on the after-noon of pro-oestrus (day 3). Ovarian histology at the day of oestrus (day 4) confirmed the presence of a low LH surge as, besides ruptured follicles, unruptured follicles with dispersion of cumulus cells were present. The pro-oestrous surge of prolactin was also advanced by 24 h. The magnitude, however, was not different from that in oil-treated rats at day 4. In conclusion, daily administration of antiprogestagens to 5-day cyclic rats results in increased basal levels of serum LH and advancement of the preovulatory surge of prolactin and LH by 1 day. The ovulatory response is low due to the low pre-ovulatory surge of LH and to a reduced ability of preovulatory follicles to respond to LH. Journal of Endocrinology (1991) 129, 423–429

1976 ◽  
Vol 70 (3) ◽  
pp. 361-371 ◽  
Author(s):  
P. C. B. MACKINNON ◽  
J. M. MATTOCK ◽  
M. B. TER HARR

SUMMARY Serum LH, FSH and prolactin levels were measured in blood samples which were obtained by decapitation from groups of female, neonatally androgenized female and male Wistar rats at 2-day intervals from birth to maturity. An increase in serum FSH levels was observed between 4 and 24 days of age in both the female and androgenized female groups, while a much later increase, between 28 and 44 days of age, occurred in the males. Serum prolactin levels increased gradually from birth in all three groups until adult levels were attained. In contrast, serum LH levels were in general low in all three groups of animals, although very high levels (> 7 ng/ml) were recorded in 22 out of 168 females and 8 out of 192 males between 4 and 28 days of age, as well as in adult males; occasional high LH levels were also seen in the androgenized females. The nature of the high serum LH levels was investigated in anaesthetized and unanaesthetized immature females by serial blood sampling using a number of techniques. Unexpectedly, only three out of 58 animals had high LH levels: two of these showed an episodic form of LH release during which levels increased to peak values and then declined within a period of about 30 min. On investigation it was found that general disturbance within the 45 min before decapitation could inhibit high LH levels in females aged between 23 and 30 days.


1985 ◽  
Vol 107 (1) ◽  
pp. 113-119
Author(s):  
J. Th. J. Uilenbroek ◽  
H. M. A. Meijs-Roelofs ◽  
P. J. A. Woutersen ◽  
P. Kramer ◽  
W. A. van Cappellen ◽  
...  

ABSTRACT To determine whether the decrease in ovarian 5α-reduced androgen production before first ovulation might be caused by an increase in serum LH, prepuberal female rats were injected at 28–31 days of age with low doses of human chorionic gonadotrophin (hCG) (0·05–0·075 i.u., four times daily). This treatment resulted in ovulation of six to ten ova per rat on day 32 in all animals. Treatment with hCG resulted in a gradual decrease in ovarian content and production (i.e. content in ovary and medium after 4 h of incubation) of 5α-dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol. The ovarian content of DHT and the production of 5α-androstane-3α,17β-diol decreased within 24 h after the first injection of hCG. Oestradiol content and production increased between 24 and 48 h after the start of treatment and was maximal on day 31 (day of pro-oestrus). Activities of 5α-reductase and aromatase were measured in ovarian homogenates obtained on days 29–31. Activity of 5α-reductase in hCG-treated rats was lower than that in control rats on all days studied. Aromatase activity in hCG-treated rats increased between days 29 and 31. It was concluded that multiple injections of low doses of hCG, which may induce ovulation, cause a decrease in 5α-reduced androgen production, which is probably due to a decrease in 5α-reductase activity. The subsequent increase in oestradiol production corresponds with an increase in aromatase activity. The results indicate that the decrease in 5α-reductase activity as observed in ovaries of spontaneously ovulating rats might be caused by the gradual increase in serum LH, which has been found to occur during the last week before first ovulation. J. Endocr. (1985) 107, 113–119


1977 ◽  
Vol 84 (1) ◽  
pp. 62-71 ◽  
Author(s):  
W. Beck ◽  
S. Engelbart ◽  
M. Gelato ◽  
W. Wuttke

ABSTRACT High serum prolactin levels were induced in chronically castrated female rats by pituitary transplants from male donor rats. The typical pulsatile LH release pattern observed in castrated control rats was maintained in pituitary grafted rats, when pituitary transplantation was performed simultaneously with castration 3 months before withdrawal of the blood samples. If pituitaries were transplanted into chronically castrated rats and blood samples were withdrawn 3 days later, the pulsatile LH release was abolished and basal or moderately elevated LH levels were found. Chronically or subacutely elevated prolactin levels had no effect on high serum FSH values. Pituitary transplants into intact female rats at day 23 after birth also suppressed basal LH values for 4 days without alterating the serum FSH levels. Six and 8 days after transplantation the serum LH levels were normal. Pituitary transplantation into these immature rats advanced puberty by more than one week. These results indicate that prolactin has an antigonadotrophic effect in female rats which is directed only towards pituitary LH but not FSH secretion. The inhibitory action of high serum prolactin levels on pituitary LH release does not last longer than 4–6 days under steady state conditions, such as found in the constantly high prolactin levels due to pituitary transplants. Under natural conditions with steadily increasing prolactin levels between day 20 and puberty the effect of prolactin in inhibiting pituitary LH release may last longer. Thus, prolactin may be one of the, if not the regulator of the timing of puberty.


1965 ◽  
Vol 33 (3) ◽  
pp. 447-454
Author(s):  
M. J. K. HARPER

SUMMARY Administration of chlormadinone, an orally active progestational agent without significant oestrogenic activity, to intact immature female rats did not affect either ovarian or uterine weight significantly compared with controls. A single injection of human chorionic gonadotrophin (HCG) caused a 73 % increase in uterine weight in 24 hr. over the control value. This dose significantly increased ovarian weight and although it caused some stimulation of follicular development, ovulation during this time did not occur. When animals were treated with chlormadinone for 8 days, and received HCG on the 8th day, uterine weight was 170% greater than in the controls and 56% greater than with HCG alone. The uterine weight produced was similar to that found in animals treated with mestranol, a potent oestrogen, and HCG. In ovariectomized animals HCG did not affect uterine weight, while the small increase produced by chlormadinone was unaltered when HCG also was given. Mechanisms are discussed by which this augmentation of the uterine response to HCG might be produced. It seems most likely that chlormadinone administration causes storage of endogenous gonadotrophin in the pituitary, and that the exogenous gonadotrophin acts as the 'trigger' for the release of stored hormone, probably by a direct action on the hypothalamus.


1976 ◽  
Vol 86 (1) ◽  
pp. 127-129 ◽  
Author(s):  
P. T. McGovern ◽  
J. A. Laing

Although the administration of pregnant mares' serum gonadotrophin (PMSG) to induce superovulation is a well established procedure (see Anderson, Schultz & Melampny, 1963), the unpredictability of the response to this treatment continues to impose a constraint on the commercial application of egg transfer techniques in the large domestic animals. In sheep, the additional use of human chorionic gonadotrophin (HCG) has been mainly centred on attempts to control the time of ovulation (Ortavant, Thibault & Wintenberger, 1949; Braden, Lamond & Radford, 1960; Dziuk et al. 1964; McGovern, Williams & Hancock, 1969). However, Killeen & Moore (1970) found that the proportion of follicles which rupture was increased in PMSG-treated ewes which had been given HCG at the beginning of oestrus. The purpose of the observations recorded here was to examine the possibility that a further gain in ovulation rate in PMSG-treated sheep might be obtained with the use of luteinizing hormone releasing factor (LHRF). No attempt was made to reproduce physiological levels of the releasing factor and dosage was aimed at achieving a superovulatory effect.


Reproduction ◽  
2004 ◽  
Vol 128 (4) ◽  
pp. 379-386 ◽  
Author(s):  
K P McNatty ◽  
L G Moore ◽  
N L Hudson ◽  
L D Quirke ◽  
S B Lawrence ◽  
...  

Ovulation rate in mammals is determined by a complex exchange of hormonal signals between the pituitary gland and the ovary and by a localised exchange of hormones within ovarian follicles between the oocyte and its adjacent somatic cells. From examination of inherited patterns of ovulation rate in sheep, point mutations have been identified in two oocyte-expressed genes, BMP15 (GDF9B) and GDF9. Animals heterozygous for any of these mutations have higher ovulation rates (that is, + 0.8–3) than wild-type contemporaries, whereas those homozygous for each of these mutations are sterile with ovarian follicular development disrupted during the preantral growth stages. Both GDF9 and BMP15 proteins are present in follicular fluid, indicating that they are secreted products. In vitro studies show that granulosa and/or cumulus cells are an important target for both growth factors. Multiple immunisations of sheep with BMP15 or GDF9 peptide protein conjugates show that both growth factors are essential for normal follicular growth and the maturation of preovulatory follicles. Short-term (that is, primary and booster) immunisation with a GDF9 or BMP15 peptide-protein conjugate has been shown to enhance ovulation rate and lamb production. In summary, recent studies of genetic mutations in sheep highlight the importance of oocyte-secreted factors in regulating ovulation rate, and these discoveries may help to explain why some mammals have a predisposition to produce two or more offspring rather than one.


1983 ◽  
Vol 103 (3) ◽  
pp. 406-412 ◽  
Author(s):  
Kalle Jääkeläinen ◽  
Seppo Markkanen ◽  
Hannu Rajaniemi

Abstract. The subcellular distribution of 125I-labelled human chorionic gonadotrophin (hCG) in preovulatory rat granulosa cells was studied in vivo. Pregnant mare serum gonadotrophin-pretreated immature female rats received an iv injection of [125I]hCG a few hours before the endogenous preovulatory gonadotrophin surge. The animals were killed at 2 or 6 h after the [125I]hCG injections. Light microscope autoradiographs showed that the mural granulosa cells of large follicles were the most highly labelled cells in the ovaries. Electron microscope autoradiography was used to study the subcellular distribution of radioactivity in the mural granulosa cells. At 2 h 45% of the counted silver grains were associated with the plasma membrane and 10% with the lysosomes, at 6 h the values were 51% and 9%, respectively. The distribution of the observed silver grains was compared with the generated expected source to grain pairs by computerized linear multiple regression analysis. The magnitudes of the regression coefficients revealed that the plasma membrane and the lysosomes were the only specifically 125I-labelled organelles, that a few radioactive molecules were located diffusely over the cytoplasm at 2 h and that the 125I-radioactivity of the nuclei was negligible. The present results suggest that preovulatory rat granulosa cells are in vivo able to internalize into lysosomes [125I]hCG initially bound to LH/hCG receptors of the plasma membrane.


1978 ◽  
Vol 87 (3) ◽  
pp. 617-624 ◽  
Author(s):  
P. A. Torjesen ◽  
R. Dahlin ◽  
E. Haug ◽  
A. Aakvaag

ABSTRACT Immature female rats were pre-treated with pregnant mare's serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) to achieve superluteinization. Eight days after the HCG administration luteolysis was induced by sc injection of 5 μg of the prostaglandin F2α (PGF2α) analogue cloprostenol (Estrumate®). The serum levels of progesterone, 20α-dihydroprogesterone (20α-DHP), prolactin (PRL) and luteinizing hormone (LH) as well as the number of ovarian LH binding sites were measured during the first 23 h after cloprostenol injection. The serum levels of progesterone decreased from 500 to 200 ng/ml within 25 min after cloprostenol administration. A further decrease to 20 ng/ml occurred during the next 4 h, and serum progesterone remained low for the rest of the period. An increase in serum prolactin (PRL) to values between 28 and 44 ng/ml was observed after 3 h and the values remained elevated for the next 7 h. Although the serum levels of progesterone declined immediately, the serum 20α-dihydroprogesterone (20α-DHP) levels remained at 60 to 140 ng/ml for the first 5 h and then gradually increased to values corresponding to the initial progesterone levels 14 to 23 h after treatment. The number of ovarian LH binding sites was between 1.2 and 1.4 × 10−12 mol/mg protein during the first 9 h after prostaglandin (PG) injection, and then decrreased to 0.8 and 0.5 × 10−12 mol/mg protein at 14 and 23 h, respectively. The serum LH levels remained below the limit of detection for the assay (10 ng/ml) throughout the observation period. PGF2α injection induced the same basic changes in the serum levels of progesterone and 20α-DHP as cloprostenol treatment. Thus, the first effect of PG treatment measured was an immediate decline in the serum levels of progesterone, and this decline probably initiated the subsequent increase in pituitay PRL and ovarian 20α-DHP secretion. Therefore, the decrease in the number of ovarian LH binding sites appeared to be a consequence rather than a mediator of luteolytic effects of the prostaglandins.


1975 ◽  
Vol 67 (3) ◽  
pp. 425-430 ◽  
Author(s):  
R. P. DEIS ◽  
NIA ALONSO

SUMMARY The effect of synthetic thyrotrophin releasing factor (TRF) on serum prolactin and LH concentrations was determined by radioimmunoassay in male, cyclic and pseudopregnant female rats. A solution of TRF (0·1, 0·25, 0·5 and 1 μg/rat) was injected i.v. at 17.00 h into rats pretreated with sodium pentobarbitone at 13.00 h. A group of male rats was also treated with TRF at 11.00 h after pretreatment with sodium pentobarbitone at 07.00 h. Fifteen minutes after TRF administration, blood samples were obtained by heart puncture. Doses of 0·25, 0·5 and 1 μg TRF significantly increased the serum prolactin concentration in pro-oestrous rats. The mean serum prolactin level after the injection of 0·5 and 1 μg into oestrous rats and 0·5 μg TRF into dioestrous day 2 rats, was significantly greater than the control values. Injection of TRF on day 1 of dioestrus had no effect. Serum LH concentration was not significantly modified by the various doses of TRF administered. On day 3 of pseudopregnancy a significant increase of serum prolactin values was obtained with 0·5 and 1 μg TRF. On day 7 of pseudopregnancy a dose of 0·5 μg produced the same effect, but on day 10 of pseudopregnancy only 1 μg TRF significantly increased serum prolactin levels when compared with the control rats. In male rats serum prolactin concentration was significantly greater than the control values after TRF treatment either in the morning or the afternoon. The response was similar to that obtained in pro-oestrous rats. The results suggest that the ability of synthetic TRF to stimulate prolactin release exists in both female and male rats and that TRF does not affect LH secretion.


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