EXPERIMENTAL STUDIES ON THE EFFECT OF ERGOCORNINE METHANESULPHONATE ON THE LUTEOTROPHIC FUNCTION OF THE RAT PITUITARY GLAND

1962 ◽  
Vol 41 (3) ◽  
pp. 321-335 ◽  
Author(s):  
G. H. Zeilmaker ◽  
R. A. Carlsen

ABSTRACT The effects of a single administration of 1 mg ergocornine methane-sulphonate to female rats with functional corpora lutea have been studied. It was shown that: 1) Injection of ergocornine into hypophysectomized rats bearing an autotransplanted pituitary brought about morphological changes in the corpora lutea; 2) In intact rats bearing two isologous pituitaries a prolonged period of leucocytic vaginal smear was found following an ergocornine-induced oestrus, indicating that the secretion of luteotrophic hormone was resumed after drug treatment; 3) Administration of ergocornine to lactating rats temporarily inhibited milk production, the effect being prevented by treatment with luteotrophic hormone. These studies indicate that the effects of ergocornine administration to intact female rats such as failure to develop decidual tissue as a response to uterine traumatization and the interruption of the leucocytic vaginal smear by oestrus, are the result of a temporary inhibition of the secretion of luteotrophic hormone by the pituitary. This brings about irreversible changes in the corpus luteum. The subsequent progesterone deficiency is responsible for the failure of the decidual tissue to develop and for the onset of oestrus three days after the administration of the drug.

1969 ◽  
Vol 60 (2) ◽  
pp. 184-198 ◽  
Author(s):  
Sidney J. Stolzenberg ◽  
Robert G. Eggert ◽  
Wayne H. Linkenheimer

ABSTRACT Female rats received pituitary autotransplants beneath the kidney capsule at 11 to 12 weeks of age or were hypophysectomized only at the metoestrous stage of the cycle. Subcutaneous injections of oestradiol benzoate (OB) were started 30 to 40 days following surgery in the first 3 experiments. In Experiments 1 and 2, Series 1 injections consisted of 50, 50 and 25 μg of OB given subcutaneously on days 0, 3 and 5. Series 2 injections were the same as Series 1 but given on days 16, 19 and 21. Pituitary grafts were removed from half of the rats on day 15 in Experiment 1. Ovarian weights were obtained on day 28. In Experiment 3, the dose of OB was raised to 100 μg per injection giving a total of 300 μg for each series. In Experiment 4, hypophysectomized rats without pituitary autotransplants were given Series 1 and 2 OB injections at the level of 125 μg per series. In Experiment 5, subcutaneous injections of OB were started 5 to 7 days following pituitary autotransplant. Rats were injected daily with 50 μg for 5, 10, 20, 40 and 80 days, with autopsies following 4 or 5 days after the last injection. In Experiment 6, 50 μg was injected daily in hypophysectomized rats without pituitary transplants for 5 and 20 days. The immediate effect of OB injections into rats bearing pituitary autografts was a significant (P < 0.01) increase in ovarian weight. Long term treatment (> 40 days) caused a significant (P < 0.05) decrease in ovarian weight. Short term treatment followed by a 23 or 35 day period of no treatment gave an even greater decrease in ovarian weight (P < 0.01). Hypophysectomized rats showed no effect on ovarian weights with similar OB treatments, indicating the importance of the pituitary gland in this response. Removal of the autotransplanted pituitary gland 10 days after the first series was completed, had no apparent effect on regression of the corpora lutea. There was no effect on adrenal weight in any of the experiments. It is suggested that oestrogens initiate a process which ultimately results in luteal regression in rats bearing pituitary autografts.


1968 ◽  
Vol 58 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Sidney J. Stolzenberg ◽  
Lloyd C. Faulkner ◽  
William Hansel

ABSTRACT Mature cycling female rats received pituitary autografts beneath the kidney capsule or were hypophysectomized only. Intraperitoneal injections of vasopressin at the level of 3 or 4 IU twice daily into rats with autografts caused an increase in adrenal weights after 45 (P < 0.01) and 70 (P < 0.01) days of treatment. There was an increase in the width of the combined zona fasciculata and reticularis observed after 70 days (P < 0.01). These results were accompanied by a decrease in ovarian weight after 45 (P < 0.01) and 70 (P < 0.01) days of vasopressin treatment. The decrease in ovarian weight was due to histologic regression of corpora lutea. Similar injections of vasopressin into hypophysectomized rats for 45 days were without effect on the ovaries or adrenals. Intraperitoneal injections of 3 or 4 IU oxytocin twice daily for 45 days in rats bearing pituitary autografts had no effect on adrenal weight or histology and caused a non-significant decrease in ovarian weight but had no effect on ovarian histology. However, after 70 days of treatment with oxytocin, there was an increase in adrenal weight (P < 0.01) which could not be attributed to an effect on the zona fasciculata-reticularis. There was a decrease in ovarian weight (P < 0.01), similarly attributable to a regression of the corpora lutea. None of the treatments affected uterine weight or histology or thyroid histology in either rats with pituitary autografts or in animals that were simply hypophysectomized. None of the treatments had any obvious effect on the cytologic appearance of the pituitary graft. It is suggested that effective treatments modified the secretory pattern of pituitary grafts.


1963 ◽  
Vol 43 (2) ◽  
pp. 246-254 ◽  
Author(s):  
G. H. Zeilmaker

ABSTRACT The functional activity of artificially induced corpora lutea in isologous ovaries transplanted into castrated male rats has been studied. Criteria for progesterone production were the morphology of vaginal transplants and the distribution of sudanophilic material in the corpus luteum cells. It was found that spontaneous functional activity of the corpora lutea did not occur in short-term experiments. Progesterone production was observed, however, in animals also bearing an isotransplanted (either male or female) pituitary gland, and in animals which received daily injections of reserpine. It is suggested that the normal influence of the central nervous system on the secretion of luteotrophic hormone is inhibitory in male as well as in female animals. Some aspects of the induction and maintenance of luteal function in castrated male rats bearing a transplanted ovary have been studied and compared with similar phenomena in the female rat. A real pseudopregnancy, i. e. maintained by the pituitary in situ during a defined period, as can be observed in female rats, could not be induced in these animals. In animals also bearing an isografted pituitary gland, luteolysis was not observed in experiments lasting up to 45 days. It is suggested that these findings may be correlated with the way in which the luteinizing hormone is secreted in the male rat.


1963 ◽  
Vol 204 (6) ◽  
pp. 1023-1027 ◽  
Author(s):  
B. D. Smith ◽  
J. T. Bradbury

Hypophysectomized or intact immature female rats were given follicle-stimulating hormone (FSH), pregnant mare's serum gonadotrophin (PMS), human chorionic gonadotrophin (HCG), or luteinizing hormone (LH) for 3 days, with or without prior administration of diethylstilbestrol for 2 days. Priming with estrogen augmented the ovarian weight response produced by FSH or PMS in both hypophysectomized and intact animals. In contrast, estrogen pretreatment enhanced ovarian growth in intact rats given HCG or LH, but not in hypophysectomized animals similarly treated. Longer periods of priming also failed to augment the ovarian response to HCG in hypophysectomized rats. The ovaries of intact rats given diethylstilbestrol and FSH contained many corpora lutea, whereas luteinization was never noted in hypophysectomized animals similarly treated. Ovarian weight augmentation in the latter was due to enhanced follicular growth throughout the ovary. Estrogen and HCG produced cystic, luteinized follicles in intact rats, in contrast to the lack of such follicular stimulation in hypophysectomized animals. It is concluded that estrogen increases the ovarian response to gonadotrophins by 1) directly stimulating granulosal proliferation, and 2) effecting the release of endogenous gonadotrophins from the pituitary gland.


1982 ◽  
Vol 99 (3) ◽  
pp. 437-442 ◽  
Author(s):  
R. J. C. van Straalen ◽  
G. H. Zeilmaker

Abstract. In this study the effects of hypophysectomy and autotransplantation of the pituitary gland on the concentration of hCG-binding sites (LH-receptors) and steroidogenesis in the corpus luteum and the testis of the rat were investigated. It was found that during pseudopregnancy both hCG-binding to homogenates of isolated corpora lutea and the progesterone levels in blood increase until day 7 and subsequently decrease until day 13. Hypophysectomy on day 5 led to a decrease of the number of LH-receptors and the serum progesterone level. By contrast hypophysectomy followed by autotransplantation of the pituitary gland increased the LH-receptor concentration and progesterone synthesis in spite of non-detectable LH-levels. Progesterone implants in hypophysectomized rats did not influence the number of LH-receptors. Hypophysectomy on day 0 without pituitary gland transplantation did not prevent the formation of some luteal LH-receptors measured on day 5 although progesterone was not secreted. A similar effect of prolactin secreted by pituitary autografts on LH-receptors was seen in the testis. The rapid decline of the number of binding sites normally observed after hypophysectomy was prevented by the presence of two pituitary autografts. Testosterone and LH-levels were non-detectable in the operated male rats. These data show that progesterone secretion by the corpora lutea is always associated with the presence of LH-receptors, regardless whether serum LH-levels are detectable or not. Moreover it appears that prolactin maintains or even increases the amount of LH-receptors in hypophysectomized male and female rats.


A number of workers have reported on replacement therapy in hypo-physectomized animals. Cushing (1912) found that pituitary transplantations prolonged the life of hypopsectomized dogs. Smith (1927) studying rats showed that the characteristic disabilities arising from hypophysectomy in rats could be completely, or almost completely, relieved by daily pituitary implants. On the other hand, intraperitoneal injections of saline extracts not only did not restore the atrophied sex organs, but prevented their repair by the pituitary implants, Putman, Teil and Benedict (1928) stated that growth was restored in hypophysectomized dogs and rats by alkaline extracts of pituitary tissue. Reichert (1928) reported successful replacement therapy in an hypophysectomized puppy with daily fresh heterotransplants of rabbit pituitary, and in a later paper (1929), growth in hypophysectomized puppies exceeding that of normal controls, after administration of Evans' extract. Reichert and others (1932) described prolan (pregnancy urine extract) as being ineffective in three hypophysectomized dogs and one rat. More recently Collip and others (1933, a, b, c ) have reported tire results of placental extracts on a large number of hypophysectomized rats. They confirmed Smith's earlier Endings (1927) and also stroked that tire response of tire hypophysectomized female rat to A. P. L. is conditioned by the state of the ovary at the time of operation. The placental material was found to lead to thecal luteinization both in the prepubertal and in the hypophysectomized animal, a conclusion reached earlier by Noguchi (1931). Collip and others were able to obtain follicle maturation and corpus luteum formation in hypophysectomized female rats by tire combination of A. P. L. and certain extracts of pituitary, and they assume that a "complementary substance" is furnished by the pituitary which cooperates with the placental substance in its action on the ovary. In two recent papers Smith and Leonard (1933) and Leonard and Smith (1933) have studied the action of a pregnancy urine extract in hypophysectomized male and female rats. In the male they obtained a beneficial effect on spermatogenesis as a result of treatment, and in the female a cornified vaginal smear and enlargement of the ovaries, which, however, decreased with continued injection. In recently operated animals there was hypertrophy of the interstitial cells and development of new corpora lutea where treatment was postponed some interstitial hypertrophy and often corpora lutea formation occurred. The present paper deals with results of treatment of 7 hypophysectomized ferrets with: (1) an anterior pituitary extract; (2) pregnancy urine extract; and (3) the two combined.


Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.


Author(s):  
T. M. Crisp ◽  
F.R. Denys

The purpose of this paper is to present observations on the fine structure of rat granulosa cell cultures grown in the presence of an adenohypophyseal explant and to correlate the morphology of these cells with progestin secretion. Twenty-six day old immature female rats were given a single injection of 5 IU pregnant mares serum gonadotropin (PMS) in order to obtain ovaries with large vesicular follicles. At 66 hrs. post-PMS administration (estrus indicated by vaginal smear cytology), the ovaries were removed and placed in a petri dish containing medium 199 and 100 U penicillin/streptomycin (P/S)/ml. Under a 20X magnification dissecting microscope, some 5-8 vesicular follicles/ovary were punctured and the granulosa cells were expressed into the surrounding medium. The cells were transferred to centrifuge tubes and spun down at 1000 rpm for 5 mins.


1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).


1961 ◽  
Vol 36 (2) ◽  
pp. 180-184 ◽  
Author(s):  
Béla Flerkó ◽  
Vera Bárdos

ABSTRACT Absence of compensatory ovarian hypertrophy in »constant oestrus rats« from lesions in the anterior hypothalamic area suggests that nervous elements localized in this region play an essential role in the stimulation of gonadotrophin output by diminution of the blood oestrogen level. The constant vaginal oestrus after unilateral ovariectomy in the majority of animals was, however, repeatedly interrupted by vaginal smears of a dioestrous type. The appearance of a dioestrous vaginal smear in the »hypothalamic constant oestrus rats« is often associated with some luteinisation. It is assumed that diminution of the blood oestrogen level by reduction of ovarian tissue in these animals may bring about a release of LH sufficient to cause formation of corpora lutea.


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