Constant Estrus Research Articles

Gonadotrophin content of pituitaries of rats in constant estrus induced by continuous illumination.

LH and total gonadotrophin of the anterior pituitaries of cycling rats under normal lighting and rats in constant vaginal estrus (CVE) induced by continuous illumination were compared. The ovarian ascorbic acid depletion method and the uterine weight increase in immature mice were employed for LH and total gonadotrophin assays, respectively. Most of the rats placed in constant light developed continuous vaginal cornification within 30 days. There was an increase in pituitary weight and the ovaries were smaller than those of the controls. The pituitary LH content and concentration were markedly decreased in rats in CVE after 50 and 100 days of illumination. Administration of progesterone, SC-13664 (an antiestrogenic compound), or clomiphene or oophorectomy caused an increase in LH. The pituitary total gonadotrophin of rats in CVE was similar to that of normal rats and increased under treatment with SC-13664 or clomiphene and after oophorectomy. Progesterone caused no change.(Endocrinology77: 529,1965)

Further studies on the hormone secretion of the anterior pituitary transplanted into the hypophysiotrophic area of the rat hypothalamus.

Anterior pituitary tissue was transplanted into different parts of the hypothalamus and other parts of the brain or under the renal capsule in hypophysectomized male and female rats. Hormone secretion by the grafted pituitary was assessed by evaluating the structure and function of the gonads, thyroids and adrenals 2-3 months after grafting. The state of the target glands depended entirely on the location of the pituitary transplant. If the pituitary was situated in the medial basal hypothalamus (the hypophysiotrophic area) gonadotrophic hormone secretion was nearly normal: the weight of the ovaries was normal and they contained ripe follicles and fresh corpora lutea; vaginal smears revealed the reappearance of nearly normal cycles after variable time intervals following hypophysectomy and pituitary transplantation; anterior hypothalamic lesions induced constant estrus, and compensatory hypertrophy of the ovary developed following unilateral ovariectomy. Direct contact with the capillary loops of the medi...

Luteinization of follicle cysts in rat ovaries as an effect of potassium iodine administration

Following X-irradiation or subtotal castration rats developed follicular cysts of the ovaries; this was accompanied by hyperestrogenism of the organism manifested in the appearance of a constant estrus. In connection with the fact that the development of follicular cysts was caused by insufficiency of the luteinizing function of the hypophysis an attempt was made to stimulate the luteinizing hormone production by microdoses of potassium iodine. The daily administration of KI in a dose of 500 γ provoked within 2 weeks luteinization of follicular cysts and their transformation into corpus luteum. Luteinization of the cysts was accompanied by a marked reduction of the body estrogen level, as manifested by the arrest of estrus with subsequent normalization of the estral cycle or a prolonged diestrus.

Luteinizing hormone release by cerebral cortex stimulation in rats.

Depletion of ovarian ascorbic acid from highly luteinized ovaries from rats was used as an index of endogenous liberation of luteinizing hormone (LH). When, in such rats, 2 µl of hypertonic saline was injected in the cerebral cortex, significant depletion of ovarian ascorbic acid took place compared with control animals. This stimulus was equally effective in different areas of the cortex that were explored. The mere implantation of the needle gave the same results. Procaine, added at 5% concentration to hypertonic saline, completely blocked cortical stimulation. The same effect was obtained by subcutaneous injection of estradiol benzoate (50 µg) or progesterone (1 mg). In animals with constant estrus, elicited by suprachiasmatic lesion, the response to cortical stimulation was blocked, but not completely. In these animals, however, an intense depletion of ovarian ascorbic acid was obtained by electrical stimulation of the hypothalamus. In animals with constant estrus, induced by injection of testosterone on the 2nd day after birth, the response was also affected. It is concluded that stimuli starting from the cerebral cortex can reach the hypothalamus and induce release of LH.

Transplantation of the ovary to the spleen in rats with persistent estrus resulting from hypothalamic lesions.

Persistent estrus has been induced in rats by electrolytic lesions located in the anterior hypothalamus. After 1 month of continuous vaginal cornification the ovaries contained large and cystic follicles but no corpora lutea. The lesions have thus disturbed the mechanism of rhythmic LH release that causes ovulation. These animals were then ovariectomized, 1 ovary being transplanted into the spleen; 1 month later the grafts showed regularly an intense luteinization. The anterior lobe of the pituitary contained numerous castration cells. Thus, estrogen deprivation induces LH release in constant estrus resulting from hypothalamic lesions. It is suggested, in agreement with Barraclough and Gorski that 2 regions within the hypothalamus control the gonadotrophic activity of the hypophysis. One is responsible for the cyclic ovulating LH discharge. The other one, more posteriorly located releases LH continuously. Its activity is depressed by estrogen.

Estrogen therapy in immature female rats with posterior hypothalamic lesions.

SummaryTwenty, 21-day-old female albino rats were subjected to bilateral lesions of the region of the mammillary bodies. Within one day of receiving a repository dose of 0.5 μg of estradiol valerate, all 6 recipients showed vaginal opening with subsequent constant estrus and reproductive organ growth. Four animals receiving sesame oil and 8 receiving no treatment exhibited definite signs of delayed puberty and reproductive organ immaturity. These results indicate the inability of the prepuberal hypothalamus to elaborate or secrete those neurosecretory substances essential for the functional sexual state of the mammal, and the dependence of estrogen secretion upon normal hypothalamic activity as mediated via the hypothysis.

Absence of compensatory ovarian hypertrophy in rats with anterior hypothalamic lesions.

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.

Anti-gonadotrophic activities of quinones and related compounds.

THE normal reproductive processes in experimental animals are reported to be altered markedly by administration of 2,6-dimethylhydroquinone (DMHQ), a possible constituent of the pea Pisum sativum Linn. (Sanyal, 1952), and by extracts of various species of Lithospermum (Cranston, 1945; Zahl, 1948; Noble, Plunkett and Taylor, 1950). A crude tea prepared from the latter plant has been used by the American Indian in the past as an oral agent to achieve temporary sterility (Train, Henrichs and Archer, 1941). Inclusion of Pisum sativum Linn, in the diet of rats was found to induce sterility (Nag and Pain, 1935–36), while injections of the extracted oil produced constant estrus (Sanyal, 1950). The simultaneous injection of this oil and chorionic gonadotrophin in the immature rat resulted in the negation of the usual gonadal response induced by the hormone alone (Sanyal, 1950). Similarity in the anti-gonadotrophic activity of these materials of diverse botanical origin is evident in their ability, upon in vitro mixture with pregnant mare serum gonadotrophin (PMS)

Development of adrenal cortical adenomas in ovariectomized mice injected with physiologic doses of sex hormone.

Since the development of adrenal cortical adenomas in gonadectomized mice has been inhibited by the implantation of pellets of estrogenic hormone, it might be inferred that withdrawal of gonadal secretion is of primary importance in precipitating the development of the castration-induced adenoma of the mouse adrenal cortex. The objective of the experiments being reported was to determine the effect of the administration of regulated, “physiologic” amounts of estrogenic or androgenic hormone on the induction of adrenal cortical tumors in susceptible ovariectomized mice. Mice of the NH strain were used in these experiments. NH females develop adrenal cortical tumors spontaneously following ovarian regression, and precociously if gonadectomized. Adrenal cortical adenomas are present in most NH mice of both sexes 5 months after removal of the gonads. Four NH males and one female whihc had been gonadectomized at 23 days of age received (by subcutaneous injection beginning 2 weeks after operation) 0.05 microgram of estradiol dipropionate in sesame oil at intervals of from 5 to 9 days. This treatment with estrogenic hormone provided for constant estrus, as determined by vaginal smear. These 5 animals were autopsied 6 months after the institution of hormone treatment. Administration of hormone was suspended 53 days before autopsy in 2 NH females which received similar treatment. Two ovariectomized NH females received the same treatment with the estrogen and in addition were injected weekly with 150 μg of progesterone in oil. Two additional ovariectomized females received the estrogen plus progesterone, but treatment was suspended 47 days before autopsy. Two NH females ovariectomized at 21 days of age were given 17.5 μg of testosterone propionate in oil weekly by subcutaneous injection beginning 2 weeks after operation. This treatment was continued until the animals were autopsied 5 1/2 months after ovariectomy. Three mice were similarly treated except that they received no injections of hormone for the 46 days preceding autopsy.

Production of Mammary Carcinomas in Male Mice With a Single Implantation of Oestrone

Several studies have shown that treatment with estrone produces mammary tumors in male mice of the R3 strain in which about 70% of the females develop spontaneous mammary carcinoma. The author experimented with 7 normally ovulating females which were implanted with very small estrone crystals. Daily smears showed all the animals to be in constant estrus until the day of death. 21 male mice of the R3 strain died before 100 days all showing signs of urinary obstruction; 2 animals developed large mammary carcinomas and in both there was a very marked enlargement of the pituitary. Both carcinomas were produced much sooner than any such tumor occurred spontaneously in the female mice. 1 of the tumors was transplanted into 6 male mice of the same strain and grew readily in all. Mammary carcinoma does not seem to occur spontaneously in male mice.

Experimental "Constant Oestrus" and the Notion of Anti-Gonadotropic Hormones.

SummaryParabiotic twins of rats exchange daily about 150 cc. of blood. If one member of a female pair is hypophysectomized it exhibits deficiencies which prove that blood received from the normal mate carries not enough hormones to maintain body weight, thyroids, adrenals and ovaries at normal levels. Castration or sterilization of males and females increases the output of follicle-stimulating hormones to the extent that normal or hypophysectomized twin females go into a condition of constant oestrus. The ovaries are visibly overstimulated and contain large follicles but no corpora lutea. Uterus and vagina exhibit also the characteristics of a maximal or even an exaggerated oestrus condition, indicating the release of large amounts of oestrin by the ovaries. Not enough oestrin accumulates in the castrate member to prevent complete atrophy of the secondary sex characters. This indicates rapid disappearance even of high amounts of oestrin from the circulation. Constant oestrus with a moderate degree of ovar...

Gonadotropic Effects in Hypophysectomized Female Rats of Implants of Pituitaries from Castrated Males

Studies of female rats united parabiotically with castrated males have shown that they are characterized by constant estrus and that their ovaries contain only large follicles (Witschi and others). The phenomenon appears to establish the actual secretion into the blood stream of the follicle stimulating hormone only on the part of the pituitary of the castrated male parabiont. The present study shows that the pituitaries of such castrated males nevertheless contain or “house” appreciable amounts of luteinizing hormone. Young mature males were castrated and after 40 days their pituitaries were implanted into hypophysectomized females 26 days of age. While a dose level was found in which follicles only occurred in the ovaries of the hypophysectomized recipients, double this dose (4 glands) led to the appearance of corpora lutea. Implants of the hypophyses from normal litter brothers produced only follicles at both dose levels. Parallel experiments with normal recipients showed that corpora were produced by both levels of castrate and normal hypophyses. The luteinizing effect of castrate male hypophysis as tested by implantation, therefore, contrasts with the results obtained by parabiosis. The explanation offered for the difference is that the absorption of the implant frees the factor responsible for luteinization, whereas this substance is retained in vivo by the hypophysis of the parabiont.

Origin of Functional Differences Between Male and Female Hypophyses.

SummaryTransplantation of testes of newborn males into the neck region of littermate females gives “takes” in 80% of the cases. In 48% the grafts do not interfere with normal endocrine or reproductive functions of the carrier, while in 32% the implanted testis assumes control of the sexual differentiation of the hypophysis. The male type hypophysis stimulates follicular development but not luteinization in the host ovary. These hosts start constant oestrus and maintain this condition after the removal of the testicular graft. It is concluded (1) that the cases with “constant oestrus” are those in which the implanted testis is sufficiently active to have a leading influence upon the hypophysis which responds with the male type of constant non-cyclic function; (2) that the hypophysis is permanently altered; (3) that the sex type of the hypophysis is secondary, depending upon the presence of differentiated sex glands.