Pregnancy Urine Extract Research Articles

The Use of Gonadotropic Hormones in the Treatment of Undescended Testes: Preliminary Report

Smith and Engle have shown that the injection of extracts of the anterior lobe of the pituitary into immature animals produces an increased growth of all the tissues of the testes, and, as a result of stimulation of the interstitial tissue, enlargement of the penis and accessory genital glands. Spermatogenesis is not produced in immature mammals by means of these extracts. Similar results are obtained with extracts of pregnancy urine, the gonadotropic principle (A.P.L. or anterior-pituitary-like hormone) of which is probably derived from the placenta. Engle has also shown that the injection of extracts of anterior lobe or of pregnancy urine causes descent of the testes in immature monkeys, in which animals they are situated in the inguinal canal.Eleven patients with undescended testes, aged 4(1/2) to 15 years, have been treated with the gonadotropic hormones extracted from pregnancy urine. The dose used in most cases was 500 rat units injected intramuscularly twice weekly. Five of the patients had bilaterally undescended testes: during treatment both testes descended into the scrotum in two cases, one descended in each of two cases, and in the remaining case the position of the testes is unchanged. The remaining six had unilaterally undescended testes; of these, three have descended into the scrotum. Thus, nine of sixteen undescended testes have entered the scrotum during treatment. The time taken to effect this change varied from two to eleven weeks. The testes which have not yet responded have received treatment for from three to nine weeks. The mechanism whereby the descent is brought about is unknown.In view of the rather unsatisfactory surgical results, it is felt that in the treatment of undescended testes a trial should be made of this form of therapy before surgical measures are considered.

OBSERVATIONS OF REMISSIONS IN HYPERTHYROIDISM INDUCED BY PREGNANCY URINE EXTRACT

Excerpt Two years ago the administration of pregnancy urine extract (Antuitrin S)†to patients with hyperthyroidism was begun in this Clinic.‡A summary of metabolic results has been reported.1In som...

Morphological Comparison of Anterior Pituitaries of Normal Castrated Female Rats and Those Receiving Injections of Pregnancy Urine Extracts.

It has been reported by Severinghaus and Wolfe, Ellison and Rosenfeld, that while injections of extracts of pregnancy urine result in marked changes in the anterior pituitaries of normal female rats, such extracts are without action on the anterior pituitaries of castrated female rats. In our previous reports, detailed data were not given; in this report we wish to present quantitative data which demonstrate that the anterior pituitaries of non-injected castrated female rats (both mature and immature) are morphologically indistinguishable from those of female rats receiving injections of extracts of pregnancy urine. Sixty-five virgin mature and 31 immature female rats were castrated. The mature females were sacrificed at 15 and 30 day intervals after operation. Forty-one of these rats received from 25 to 75 units of an extract of pregnancy urinet daily throughout the 15 day castration period or for the last 15 days of the 30 day castration period in those rats which were sacrificed after 30 days. All immature rats were between 25 and 30 days old at operation, and were sacrificed 15 days after operation. Sixteen received 25 units of pregnancy urine extract daily for the entire period; 15 littermate sisters served as controls. At autopsy the pituitaries were weighed and fixed in Regaud's fluid. Serial sections of all glands were cut. Complete cell counts were made on 5 sections from each of the 90 glands, A total of 331,056 cells were counted. The quantitative results of these studies are presented statistically in Table 1. (Frequency distribution, means and standard deviations are given). Analysis of this table reveals that the percentages of the various cell types in the anterior pituitaries of the injected rats were almost identical to the percentages of these cells in the anterior pituitaries of the control rats castrated for a similar period of time.

Anterior Pituitaries of Infantile Female Rats Receiving Injections of Pregnancy Urine Extract.

Anterior Pituitaries of Infantile Female Rats Receiving Injections of Pregnancy Urine Extract.

Comparative Quantitative Effects of Castration in Mature and Immature Female Rats.

Ellison and Wolfe have reported that in the anterior pituitaries of castrated mature female rats there is an increase in the percentages of the basophiles to a mean level of 9% in the 15-day castrates and 13.6% in the 30-day castrates. A few signet-ring castration cells were also found in the anterior pituitaries of the 30-day castrates. In further studies we have pointed out that injection of pregnancy urine extracts are without action on the pituitaries of mature female rats castrated for 15 and 30 days. By adding the 2 series of injected and uninjected animals together, we have to date studied and made cell counts on the anterior pituitaries of 25 mature females castrated for 15 days and 39 castrated for 30 days. These data are arranged in statistical form in Table I, in which the frequency distribution of the percentages of the various cell types, the mean and the standard deviation are given. In addition, 31 immature female rats were castrated when between 25 and 30 days of age and sacrificed 15 days later. Sixteen of these animals received injections of pregnancy urine extracts. Since these extracts were without action on the anterior pituitary, data from these 31 rats are considered together and arranged statistically in Table I. For non-castrated controls we have to date made cell counts on the anterior pituitaries of 69 mature female rats killed at various periods of the oestral cycle, and 31 immature female rats killed between 25 and 35 days of age. The mean levels of the eosinophiles in the anterior pituitaries of the mature and immature controls were 33.6 and 36.1%, respectively. The standard deviations (S. D.) were 4.5 and 3.9, respectively.

Morphological studies on the anterior pituitaries of mature female rats receiving injections of pregnancy urine extracts

Morphological studies on the anterior pituitaries of mature female rats receiving injections of pregnancy urine extracts

Cytological studies on the rat pituitary after injections of pregnancy urine extract and pregnancy blood serum

Cytological studies on the rat pituitary after injections of pregnancy urine extract and pregnancy blood serum

THE PRODUCTION OF TESTICULAR DESCENT WITH THE WATER-SOLUBLE (ANTERIOR PITUITARY-LIKE) FRACTION OF PREGNANCY URINE

Until relatively recent times persons lacking completely descended testes were subjected to surgical treatment for the alleviation of this condition. Those acquainted with such procedures will recall the difficulties met with and the incomplete results incident to the process of “lengthening the cord.” In 1930 Schapiro subjected several adolescent boys with incompletely descended testes to medical treatment by employing Aschheim and Zondek’s prehormone. This led to a fair degree of success. Since then Engle (1932a) succeeded in producing complete testicular descent in immature monkeys (Macacus rhesus) by the use of water-soluble fractions of pregnancy urine and anterior pituitary extract. By this method of treatment the cord lengthened naturally. In the successful instances mentioned above, however, the testes had already entered the inguinal canals before treatment was begun. Since testieular descent within the canal is believed by some to occur as a passive phenomenon as this gland enlarges and since th...

The effect of extract of pregnancy urine upon hypopituitarism in the male

Summary 1.Eight male children with hypopituitarism were treated with extract of pregnancy urine (antuitrin-S). 2.Descent of the testes was accomplished in all of three cases of cryptorchism. 3.In three cases characterized by genital underdevelopment (testes descended), treatment resulted in enlargement of the testes and scrotum and the appearance of the secondary sex characteristics. 4.In two cases characterized by pituitary obesity with normal genital development, treatment resulted in no increase in size of the genitals. 5.In four of five cases receiving basal metabolism tests before and at the end of treatment, the basal metabolic rates were lowered below the lower limits of normal at the end of treatment. 6.The inconsistency of the change in blood cholesterol level following treatment does not permit definite conclusions. 7.In five cases receiving sugar tolerance determinations before and at the end of treatment, the tolerance was lowered at the end of treatment. 8.In seven of the eight cases, there was an increase in growth of stature above the normal for the age following treatment. 9.In our series of cases, antuitrin-S did not stimulate weight loss and did not alter the typical pituitary distribution of fat. Summary 1.Eight male children with hypopituitarism were treated with extract of pregnancy urine (antuitrin-S). 2.Descent of the testes was accomplished in all of three cases of cryptorchism. 3.In three cases characterized by genital underdevelopment (testes descended), treatment resulted in enlargement of the testes and scrotum and the appearance of the secondary sex characteristics. 4.In two cases characterized by pituitary obesity with normal genital development, treatment resulted in no increase in size of the genitals. 5.In four of five cases receiving basal metabolism tests before and at the end of treatment, the basal metabolic rates were lowered below the lower limits of normal at the end of treatment. 6.The inconsistency of the change in blood cholesterol level following treatment does not permit definite conclusions. 7.In five cases receiving sugar tolerance determinations before and at the end of treatment, the tolerance was lowered at the end of treatment. 8.In seven of the eight cases, there was an increase in growth of stature above the normal for the age following treatment. 9.In our series of cases, antuitrin-S did not stimulate weight loss and did not alter the typical pituitary distribution of fat.

Studies on Ovarian Inhibiting Action of Certain Pituitary Extracts

It has been amply demonstrated that hypophyseal extracts containing the growth principle will prevent the gonad-stimulating action of hypophyseal or pregnancy urine extracts in immature or hypophysectomized rats (Smith, Evans, Reiss and Leonard). This inhibitory action was first ascribed by Evans and his coworkers to the growth hormone but later work led them to abandon their original thesis. Investigations along similar lines also indicated that the growth hormone is not the antagonistic principle. Results obtained on the study of this reaction constitute this report.Sexually immature female rats were given 10 R.U. of pregnancy urine extract (Antuitrin S)† subcutaneously, which approximately doubled the weights of the ovaries in 5 days. Litter mates which were concurrently injected with pregnancy urine and extracts of beef and sheep pituitaries containing growth hormone (doses 1 cc. to 5 cc.) prepared after the method of Van Dyke,1 failed to show the increase in weight of the ovaries. The repressing effe...

Effect of Urine of Castrate Women on the Female Guinea Pig

The failure of pregnancy urine to produce morphological changes in the ovaries of guinea pigs similar to those produced in rats has been recognized by Jares, and Selye et al. In view of the recent discovery that the hormone in the urine of castrate women is different from that in pregnancy urine when tested on hypophysectomized female rats (Leonard and Smith), it seemed of interest to compare their effects on the female guinea pig. Five guinea pigs ranging from 120 to 250 gm. in weight were injected subcutaneously for 5 to 8 days with an extract of urine of a castrate woman. The amounts used, based on the equivalents of whole urine, varied from 150 cc. to 400 cc. For controls, either one ovary was removed before treatment was begun (3 cases) or comparisons were made with the ovaries of uninjected pigs of similar size. (2 cases.) Two other guinea pigs were treated with 100 R.U. and 500 R.U. of pregnancy urine extract. The ovaries, thyroids, adrenals and uterus were weighed at autopsy and the ovaries were sectioned for further study. In all cases, the ovaries of the animals receiving the urine of castrate women increased in size and showed very marked follicular development. For example, in 3 young guinea pigs, the control ovaries weighed 29.6 mg., those of the animal receiving 200 cc. equivalent of urine weighed 39.6 mg., and those of the animal receiving 400 cc. equivalent weighed 80.3 mg. The uteri in all cases were markedly enlarged and the vaginas were open. In the ovaries of the largest animal, corpora lutea were found, none being present in the controls. Thyroids and adrenals were not significantly increased in size. These results, while not based on a large number of animals, were all consistent in producing the follicular stimulating effect which is characteristic of such urines and is in marked contrast to the effects of pregnancy urine. The guinea pig, like the hypophysectomized rat, can be used qualitatively to differentiate the urinary gonadotropic hormones.

Prolonged Pregnancy in Albino Rat following Injection of Pregnancy Urine Extract

ConclusionProlongation of pregnancy with development of fetuses of excessive size was regularly observed in rats following a single injection of 75 rat units of urine extract administered 4 days before term.Previous observers have found marked alterations in the termination of pregnancy in the rat, following (1) injections of extracts of the corpus luteum (Nelson, et al.1), (2) injections of extracts of the anterior pituitary (Teel,2 Hain3), and implants of the anterior pituitary (Hains), (3) injections of the urine of pregnant women (Levin, et al.4 Hain3), and (4) hypophysectomy (Pencharz and Long5). The results of these investigations are difficult to evaluate in view of the differences in the substances administered, in their preparation and dosage, and in the parity and stage of pregnancy of the animals when treated.In the present experiments the attempt was made to observe the duration of pregnancy in rats injected near term with a uniform dose of urine extract. The investigation was planned to take ...

Reaction of Anterior Pituitaries of Immature and Mature Female Rats to Injection of Pregnancy Urine Extracts

It has been previously reported1 that injections of an oestrin-free placenta extract, containing the A. P. L. factor, into immature female rats induced a marked increase in the weight of the ovaries and a moderate increase in the weight of the pituitaries. Histologically, the pituitaries of the injected rats showed a slight to moderate decrease in the level of the eosinophiles; a considerable number showed evidence of granular loss. The most evident changes were found in the basophiles, which showed marked evidence of granular depletion.Injection of pregnancy urine extracts into immature female rats gives similar results. Thirty rats, 21 to 25 days old, were given daily injections of pregnancy urine extract† (25 to 75 R. U. daily for 6 to 15 days). Twenty-eight littermate sisters served as controls. The ovaries of the injected rats weighed from 50 to 80 mg., while those of the controls weighed from 15 to 25 mg. The pituitaries of the injected animals were usually, but not invariably, increased in weight. ...

MENSTRUAL RESPONSE TO LUTEINIZING EXTRACT OF PREGNANCY URINE

Hamblen (1), Novak and Hurd (2) and others describe beneficial changes in menstrual irregularities following the hypodermic injection of a luteinizing extract of pregnancy urine (Antuitrin-S, Parke, Davis & Co.).* Search of the literature revealed no observations on its effect upon normal menstruation. The present brief report deals with this relationship. A group of 10 normal women volunteered as subjects for study. Of these, only one was married. Five were medical students and four were studying physical education. Seven were in the third and two were in the fourth decades of life. The married subject was in the fifth decade. The average weight of the ten subjects was 135 pounds and their average height 5 feet 4 inches. The luteinizing extract of pregnancy urine assayed at approximately 100 rat units per cubic centimeter. The subjects received 10 injections. The first dose was 1 cc. and subsequent ones 2 cc, if this amount did not create too much local reaction. In that case a smaller dose was given. The injections were given daily, except Sunday. The total dosage varied from 12 to 20 cc, the average being 17.5 cc

Action of Pregnancy Urine Extract (Follutein) on the External Genitalia of Female Guinea Pigs.

Injections of Follutein into sexually immature female guinea pigs produce an enlargement of the clitoris. Animals treated over a long period show a considerable enlargement. The clitoris takes the form of a typical penis which protrudes when the surrounding tissues are subjected to pressure. The prepuce, the corpus cavernosum, and the glans are well differentiated. The size of the enlarged clitoris is considerably smaller than the size of a male penis, in animals of corresponding age. Adult female guinea pigs treated with Follutein respond likewise, although the growth of the clitoris is less pronounced than in the young females. Experiments were made on a group of 48 animals. After the administration of 3–5 cc. of Follutein over a period of about 10 days, changes can be observed in the clitoris. These become very pronounced after a more prolonged administration over 4–6 weeks. The results do not imply necessarily a specific action. The histological examination of an experimentally enlarged penis-like clitoris reveals a general enlargement of the organ. No definite specific effect is noticeable in any of its tissues. A marked increase in circulation and pronounced swelling in the external genital region appear after treatment. Vascular changes as a result of injections of pregnancy urine have been noticed previously by Papanicolaou. He advanced the hypothesis that the luteinizing effect on the ovaries, as well as the stimulating action upon other glands, might be interpreted as being primarily due to vascular changes. Preliminary work on ovariectomized animals shows that the growth potentiality of the clitoris almost disappears after complete removal of the ovaries. There is, however, an indication of a circulatory stimulation. This suggests that at least 2 separate factors are involved. One factor induces congestion and swelling and acts primarily on the clitoris itself; the other factor induces growth and acts secondarily through the stimulation of the ovaries.

Changes in Hypophysis of Adult Male and Female Rats After Pregnancy Urine Extract Injections.

Meyer, Leonard, Hisaw and Martin1 demonstrated that oestrin diminishes the gonad stimulating capacity of the anterior pituitary. Inasmuch as the injection of P. U. extract into normal females increases their oestrin output, the potency of their pituitaries should thereby be diminished. Leonard2 injected a large series of adult male and female rats with P. U. extracts† and subsequently tested their pituitaries for gonad stimulating potency by implantation into immature female mice. Pituitaries of the injected animals showed a marked decrease in gonad stimulating potency. The potency of the castrate's pituitary was not diminished by P. U. injections.The pituitaries of 32 normal and castrate controls and injected rats, from the experiments of Dr. Leonard, were utilized for cytological study. They were fixed and stained by methods previously described.3 As expected, marked changes were observed in the basophiles.4 These cells in large part were depleted of their basophilic granules. Their cytoplasm appeared a...

TREATMENT OF SEXUAL UNDERDEVELOPMENT IN THE HUMAN MALE WITH THE ANTERIOR PITUITARY-LIKE HORMONE OF URINE OF PREGNANCY*

Since announcements by Zondek and Aschheim (1) and Smith and Engle (2) that pituitary transplants would induce precocious sexual maturity in immature rats and mice and the discovery by Zondek and Aschheim (3) of the gonad-aetivating hormone in the urine of pregnant women, a wealth of experimental knowledge on the pituitary-gonadal relationship has been developed. While Engle (4, 5) aud Evans and Simpson (6) have demonstrated clearly that the actions of pregnancy urine extracts are not identical with those of anterior pituitary transplants or extracts, their actions both as a luteinizing agent and as a gonad-activator so closely similates that of pituitary extracts that their use has been generally adopted. In fact, Engle has shown that the pregnancy urine extracts are possibly more effective than actual pituitary extracts in stimulating descent of the testes of monkeys. This indication is of the utmost significance because of the availability and universal use of the urine extract. While the greater part of the experimental work has been done on female animals, there is sufficient proof that the hormone from pregnant urine activates the jonads of both male and female.

THE EFFECT OF PREGNANCY URINE EXTRACT AND OVARIAN FOLLICULAR HORMONE ON HYPERTHYROIDISM

Clinical recognition of the importance of ovarian function in thyroid disease led us to try the effect of pregnancy urine extract containing sex gland-stimulating hormone on the course of hyperthyroidism. The preparation used was Antuitrin-S, generously furnished by Dr. E. A. Sharp of Parke, Davis & Company. This corresponds to the Prolan solution of Zondek (1) and has a strong luteinization effect on the ovaries of small animals when large doses are given, but is reported to have a follicle-ripening effect in such experiments when given in high dilutions. Its chief clinical use at present is in the control of menstrual disorders (2). Geist (3) reports that he found at operation no ovarian change in 22 patients who had been treated for two weeks with anterior luteinizing hormone. Recently Mandelstamm (4) found at operation, along with other effects, cystic follicles in the ovaries of patients treated with. Prolan but no evidence of luteinization. The solution used by us contains no thyreotropic anterior p...

COMPLETE RECOVERY OF GONADOTROPIC SUBSTANCES FROM THE URINE OF PREGNANT WOMEN*†

There are now available several methods which can be relied upon for the preparation of pregnancy urine extracts which are highly gonadotropic in character. Many of the processes are outgrowths or modifications of the one described by Zondek (1) for obtaining prolan from urine. One or more of the fundamental steps of the Zondek method are therefore common to subsequently developed procedures. Table 1 gives a synopsis of the essential steps of eight recently published methods. It may be seen that two procedures, concentration of the urine, or hormone, and precipitation of the active principle by acetone or alcohol, are employed in all of these methods. Concentration of the urine to one-eighth or to one-tenth the original volume is an advantageous procedure, from the standpoint of ease of manipulation, when extracts are to be prepared from large quantities of urine. Dickens (2), Wiesner and Marshall (3), Katzman and Doisy (4), and others effect volume reduction by distillation in vacuo at temperatures rangi...

Studies on the hypophysectomized ferret. VIII. -Effect of administration of anterior lobe extract, prolan, and the two combined

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.