Regulation of the primate fetal adrenal gland and testis in vitro and in vivo.
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Biomedical subjects
Publications and source records attributed to R B Jaffe.
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To assess intrauterine fetal testicular function, the carotid or femoral vessels of rhesus monkey fetuses, 129-145 days gestational age, were catheterized following hysterotomy of the mother. The fetus was returned to the uterus, the catheters were exteriorized through the mother's vagina and the pregnancy was allowed to continue. In this chronic preparation, basal levels of testosterone (measured with an RIA with 65% cross-reactivity with 5 alpha-dihydrotestosterone) in male fetal serum were 0.85 +/- 0.29 (SD) ng/ml. Administration of a 10 or 100 IU intra-arterial bolus of hCG into the fetal circulation stimulated in increase in fetal serum testosterone levels of 70 and 630%, respectively. Other fetuses were challenged with bolus infusions of 10 and 50 micrograms of synthetic gonadotropin releasing hormone (GnRH). The lower dose caused an increase in serum testosterone concentrations in only one of four fetuses, while the higher dose resulted in a positive response in all three experiments performed. With this dose, the mean increase in circulating testosterone concentration after 1 h was 105%. In vitro, specific binding of iodinated hCG was demonstrated in testicular homogenates from rhesus fetuses near term and hCG stimulated testosterone biosynthesis in testicular minces. Maximal stimulation was achieved at hCG concentrations between 5 and 50 ng/ml. The data indicate that the testes of fetal rhesus monkeys during late gestation are capable of androgen biosynthesis and can bind and respond to gonadotropin stimulation. Furthermore, the pituitary-gonadal axis in the fetal male monkey is capable of responding to GnRH stimulation at this stage of gestation.
The role of hCG in the regulation of testicular steroid production in human fetuses from 14 to 20 weeks gestational age was studied. Saturable binding of 125I-hCG to testicular homogenates was demonstrated, and physiologic concentrations of hCG were able to stimulate testosterone formation in testicular minces without the addition of exogenous precursors. In five fetses of 16-20 weeks gestational age, the capacity to bind hCG varied from 25.6 to 42.2 pg/mg wet tissue. The association constant of binding was 1.07+/-0.12 X 10(10) M-1. Testicular minces from six other fetuses (gestational age 14-19 weeks) were incubated in the presence of concentrations of 0, 0.5, 5 or 50 ng/ml NIH-hCG (1 mg=10,000 IU), which are within the physiologic range. Preincubation of 30 min in excess buffer was necessary to observe clear differences in testosterone production rates between controls and hCG stimulated testicular tissues. The greatest increase in testosterone production occurred when the hCG concentration was increased from 0.5 to 5 ng/ml. Little additional stimulation was observed at a concentration of 50 ng/ml. Maximal production rates of up to 12 ng/mg tissue/h were seen. It is concluded that human fetal testes bind hCG, and that physiologic levels of hCG stimulate fetal testicular testosterone formation in vitro at this stage of gestation.
The clinical records and radiographs of 46 patients with a supracristal ventricular septal defect are reviewed to illustrate the spectrum of associated lesions and complications seen with this defect. The presence of a supracristal ventricular septal defect compromises the normal conal muscular support of the aortic valve, usually in the region of the right sinus of Valsalva, and, consequently, complications involving the aortic valve are frequently noted. Decreased sinus support may lead progressively to prolapse of the right aortic cusp through the supracristal ventricular septal defect into the right ventricular infundibulum effecting sequentially aortic regurgitation, right ventricular outflow obstruction, and ultimately right sinus of Valsalva-right ventricular fistula. This potential progression is an indication for early recognition and repair of the supracristal ventricular septal defect. A supracristal ventricular septal defect is also an integral component of the Taussig-Bing malformation, is present in the majority of patients with aortic arch interruption, and may be seen in as many as 25% of Oriental patients with tetralogy of Fallot.
Abnormalities of the systemic atrioventricular (A-V) valve are frequently present in patients with corrected transposition. Systemic A-V valve regurgitation is usually present and may be amenable to operative correction with valve replacement if the regurgitation is caused by normally positioned but deformed valve leaflets or a dilated valve ring, or both. Systemic A-V valve regurgitation secondary to the more common Ebstein-type malformation of the inverted tricuspid valve is an inoperable conditon at present. Displacement of the valve leaflets below the level of the valve ring may be seen in the angiocardiograms of patients with this finding and is the differentiating feature between the two lesions. Ten cases of systemic A-V valve regurgitation in patients with corrected transposition are reviewed to illustrate these features.
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Thirteen neonates presented with central cyanosis due to right-to-left shunting across the foramen ovale or the ductus arteriosus or both. In three infants shunting occurred secondary to pulmonary vascular obstruction, presumably related to pulmonary vasospasm (persistence of the fetal or transitional circulation). In ten neonates right-to-left shunting was associated with heart failure; seven of these neonates had systemic hypotension.
Despite the efforts of a large number of investigators, the role of GnRH in clinical gynecology is uncertain. At present, its greatest utility is in research directed toward the understanding of hypothalamic-pituitary interrelationships. However, a clear understanding of the hypothalamic control of gonadotropin secretion awaits the actual measurement of the secretion of GnRH by the hypothalamus. In addition, a better understanding of the ability of the pituitary to secrete gonadotropins in various disorders of menstruation and maturation will probably be achieved through the determination of the capacity of the pituitary to synthesize as well as release gonadotropins in response to GnRH. Such determinations will probably utilize repeated or continuous infusions of GnRH rather than the currently more popular single injection technique. Finally, GnRH may be useful in the induction of ovulation. A definition of its role in ovulation induction awaits the results of additional clinical studies. Understanding of the nature of hypothalamic control of the pituitary is as yet incomplete. The availability of hypothalamic releasing factors will make it possible to study in greater detail the mechanisms by which the fine regulation of the endocrine system is achieved.
Chest roentgenograms in 13 infants and angiocardiograms in 11 infants with persistent transitional circulation (PCT) syndrome were reviewed. Chest radiographs typically revealed congestive heart failure with pulmonary venous congestion, cardiomegaly, hepatomegaly, and pleural effusions. Angiocardiography demonstrated a right-to-left shunt through the ductus arteriosus, ventricular dilatation, poor myocardial function, and ventricular emptying. Cardiopulmonary abnormalities resolved over a period of 2-6 days in survivors. PTC syndrome as seen at the authors' institution has been an important and relatively common cause of congestive heart failure and cyanosis in the newborn. The incidence of congestive failure was higher than in other reported series.
The radiographic findings in 13 patients with congenital complete heart block without associated anomalies are presented to illustrate characteristic features. Findings related to the increased stroke volume in these patients include: (a) simulated shunt vasculature; (b) pulmonary venous pypertension with redistribution of blood flow to the upper lungs, and, in one patient, peribronchial edema; (c) cardiomegaly with right ventricular, pulmonary artery, left atrial, left ventricular, and aortic enlargement; and (d) variation in cardiac size on serial examinations. Less commonly seen were findings related to atrioventricular dissociation with transitory marked pulmonary venous hypertension present in one patient when left atrial contraction occurred during ventricular systole when the mitral valve was closed.
The angiocardiograms of 17 patients with aortic arch interruption are reviewed to emphasize the variations in arch interruption and origin of the brachiocephalic vessels, and collateral circulation to the descending aorta. Depending on the anatomical type and subtype of arch interruption, collateral flow to the descending aorta in the presence of a stenotic or closed ductus will be dependent on the development of intercostal collaterals and/or the presence of retrograde flow in all brachiocephalic vessels arising from the descending aorta. Familiarity with the potential pathways for collateral circulation may permit differentiation into types and subtypes on chest radiograph. Patients with Type I interruption may have bilateral rib notching if the right subclavian artery originates normally from the innominate artery, but will have rib notching confined to the left side if the origin of the right subclavian artery is aberrant. Type II or Type III interruption patients will have rib notching confined to the right side if the right subclavian has a normal origin, but no rib notching if the origin of the right subclavian artery is aberrant.
This study was designed to investigate the effect of varying concentrations of estradiol, administered to normal women, upon the gonadotropin response to synthetic gonadotropin-releasing hormone (GnRH or LRF). Beginning at 4 pm on the first day of the menstrual cycle, 19 studies were performed in subjects who received injections of estradiol benzoate (E2B every 12 h for 6 days). Concentrations of E2B administered (mug/kg/12 h) were: 0.3, 0.6, 1.25, 2.5, 3.75, and 5.0. Mean serum estradiol concentrations achieved at these respective concentrations of E2B were 43, 53, 91, 145, 195, and 305 pg/ml. Twelve h after the last E2B injection, an intravenous bolus of 100 mug GnRH was administered. Gonadotropin response to this dose of GnRH after E2B was compared with each subject's response in the early follicular phase of a previous (control) cycle during which no exogenous estradiol was administered.
Gonadotropin responses to synthetic gonadotropin-releasing hormone (GnRH or LRF), as well as basal concentrations of gonadogropins, estradiol, and prolactin, were determined at weekly intervals during the first eight weeks post partum in seven non-nursing, non-steroid-treated women. The results were compared with those of a group of eleven women studied on the second day of the menstrual cycle. In the postpartum group, baseline concentrations of LH and FSH similar to those seen in the early follicular phase of the menstrual cycle occurred by the third week post partum. In response to an iv bolus of 100 mug GnRH, elevations of serum LH: 1) occurred as early as the second postpartum week; 2) were less than those of women during the early follicular phase until the fourth postpartum week; and 3) were exaggerated (when compared with those ob subjects in the early follicular phase) during the fifth through the eighth week post partum. Similarly, the FSH responses to GnRH in the puerperium were similar to those of the subjects during the early follicular phase by the third week post partum, and were exaggerated during the second month post partum. These studies demonstrate that human pregnancy is followed by a period of relative pituitary refractoriness followed by one of increased responsiveness to GnRH.
A 22-year-old nulliparous woman presented with primary amenorrhea, primary hypothyroidism, hyperprolactinemia, and radiologic evidence of pituitary enlargement. Investigation demonstrated limited reserves of ACTH and growth hormone. Circulating concentrations of TSH and prolactin were elevated; they increased in response to thyrotropin releasing hormone and decreased following L-dopa administration. After treatment with L-tri-iodothyronine, serum TSH and prolactin levels fell markedly, reserves of growth hormone and ACTH returned to normal, menstrual periods began, and the patient conceived. She experienced an uncomplicated prenatal, intrapartum, and postpartum course. It is thought that this patient represents a distinct clinical entity: a syndrome of amenorrhea, hyperprolactinemia, and pituitary enlargement, all secondary to primary thyroid failure. This syndrome should be distinguished from the Forbes-Albright syndrome, as it is reversible with thyroid replacement therapy. Recognition of this syndrome may thus spare the patient unnecessary, and potentially dangerous, pituitary surgery or irradiation.
Hypophyses of 21 human fetuses, ranging in gestational age from 6 to 23 weeks, were studied by immunocytochemical and histological staining to ascertain (1) the time of origin of specific cell types and (2) the development of parenchymal cell zonation in the pars distalis. No hormones were identified at six weeks. Probable corticotrophin-containing cells appeared at seven weeks. Somatotrophs were observed first at 10.5 weeks; correlation with other reports indicates that they appear at eight to nine weeks. Melanotrophs were detected at 14 weeks; the cells containing melanotrophin were far fewer than corticotrophs. The youngest fetus to possess gonadotrophs was 10.5 weeks old. In all specimens gonadotrophs (LH-cells) stained well with immunocytochemical procedures but poorly with histological methods. Thyrotrophs first occurred at 13 weeks. Zonal distribution of cell types in the pars distalis was evident almost from the time of their appearance. Somatotrophs were most numerous laterally and immediately anterior to the residual cleft. At 10.5 weeks corticotrophs were confined chiefly to the borders of vascularized connective tissue (trabeculae) and to the lateral peripheral region of the pars distalis. Thyrotrophs appeared chiefly in the anteromedian zone, particularly in its superior portion, but were found laterally also. In the older specimens, gonadotrophs generally occurred throughout the pars distalis but were less numerous near the trabeculae and in the anterolateral region. There was good correlation between the time of appearance of various cell types and published data on secretory capacity of the gland.
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The clinical presentation and characteristic radiographic and angiographic findings in 6 patients with mycotic aneurysms of the pulmonary artery of aorta are presented. Radiographic findings that may suggest a mycotic aneurysm of the pulmonary artery include a rapid change in its coutour, which may be aneurysmal in character, and multiple septic pulmonary emboli or bacterial pneumonia. Patients with mycotic aneurysms of the descending thoracic aorta may have a middle or posterior mediastinal mass in close association with the aorta, and a pulmonary infiltrate may be seen surrounding the aneurysm. A barium swallow will often demonstrate esophageal displacement by the extrinsic mass.