PubMed Health⌕ Search

Biomedical subjects

F G Cassorla

Publications and source records attributed to F G Cassorla.

At least 19 recordsLinked to original sources
PubMed1994

Estradiol inhibits growth hormone receptor gene expression in rabbit liver.

We studied the ontogeny of GH receptor mRNA levels and the effect of exogenous estradiol administration on GH receptor mRNA levels in rabbit liver. A solution hybridization-RNase protection assay revealed a predominant 370-base long protected band corresponding to the mRNA encoding the transmembrane GH receptor, and a 241-base long protected band, representing about 9.0%, with the predicted size for the truncated form of the GH receptor. To study the developmental profile of GH receptor expression, we studied 12 female rabbits, at ages 1, 3, 5 and 7 months. Maximal GH receptor mRNA levels were observed in 3-month-old animals and decreased in 7-month-old animals. To investigate the effect of estradiol, 8-week-old immature female rabbits were randomly divided into five groups, and received subcutaneous pellets containing either placebo or estradiol at doses of 0.1, 0.5, 1.5 and 5.0 mg for 3 weeks. Exogenous administration of estradiol, at doses that resulted in physiological circulating levels, induced a reduction in GH receptor expression, measured both by GH binding (36 and 46%), and GH receptor mRNA levels (38 and 87%), in animals receiving pellets containing 1.5 and 5.0 mg of estradiol, respectively. We conclude that estradiol decreases GH receptor expression in rabbit liver. The results of our study suggest that there is an inverse relationship between circulating estrogen concentrations and liver GH receptor expression.

Aging↗
PubMed1994

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys.

To determine the effects of puberty and estrogen priming on the GH response to standardized treadmill exercise and arginine-insulin in normal boys and girls, we performed tests in 84 normal children (41 girls and 43 boys) representing all stages of puberty. A subset of the prepubertal children received the tests twice, with or without the administration of ethinyl estradiol (40 micrograms/m2 daily) for 2 days before the tests. The peak GH response to the three tests increased significantly with pubertal stage (r = 0.57; P < 0.0001), but did not differ between boys and girls at the same stage. With advancing puberty, the percentage of normal children who failed to attain a GH level greater than 7 micrograms/L during any of the three tests declined from 61% at pubertal stage 1 to 44% at stage 2, 11% at stage 3, and 0% at stages 4 and 5. Administration of estrogen to the prepubertal subjects raised the normal range for the peak GH response to the three tests from 1.9-20.3 to 7.2-40.5 micrograms/L. We conclude that both puberty and estrogen administration significantly increase the peak GH response to exercise, arginine, or insulin in normal subjects. Moreover, the conventional criterion that the peak GH response to three stimulation tests should exceed 7 micrograms/L was applicable in our study only to subjects who had attained pubertal stage 4 or 5 or who had received estrogen administration.

Adolescent↗
PubMed1993

Multiple hormone deficiencies in children with hemochromatosis.

Patients with thalassemia major require multiple blood transfusions leading to hemochromatosis. These patients often have pubertal delay and growth failure, the etiology of which has not been fully elucidated. We performed an extensive endocrine evaluation which included measurements of spontaneous and stimulated levels of gonadotropins, GH, thyroid hormone, and adrenal hormones in 17 patients between the ages of 12 and 18 yr with hemochromatosis receiving desferoxamine therapy. All of the 17 patients had at least one endocrine abnormality, and 12 had more than one abnormality. Abnormalities of the hypothalamic-pituitary-gonadal axis were the most common. Six patients had clinical evidence of delayed puberty with spontaneous and stimulated gonadotropin and sex steroid levels appropriate for their delayed pubertal stage. All 14 children in puberty LH pulsatility index below the mean for pubertal stage compared to normal children. Six of the 14 had LH pulsatility index more than 2 SD below the mean for pubertal stage. This may be an indicator of abnormal pituitary function. Six patients failed either the provocative GH tests (peak GH < 7 micrograms/L) or had a mean spontaneous GH less than 1 microgram/L. The 4 patients who failed provocative tests had growth velocities more than 2 SD below the mean for bone age. Three patients had evidence of primary hypothyroidism. We conclude that all patients with hemochromatosis need periodic careful endocrine evaluations because the incidence of endocrine dysfunction is substantial and they may benefit from hormonal therapy.

Adolescent↗
PubMed1993

Effect of deslorelin-induced pubertal delay on the growth of adolescents with short stature and normally timed puberty: preliminary results.

LH-releasing hormone agonist (LHRHa) treatment slows bone maturation and improves adult height in children with LHRH-dependent precocious puberty. To determine whether pubertal delay induced by LHRHa can enhance final height in patients with short stature and a normally timed puberty, we enrolled 43 short children (28 girls and 15 boys) in a double blind, placebo-controlled trial. Patients were assigned randomly to receive either placebo or LHRHa (deslorelin), administered sc at a dose of 4 micrograms/kg.day for a period of 4 yr. This report describes the preliminary results in 16 children who have completed 4 yr of treatment (9 patients in the deslorelin group and 7 patients in the placebo group). Predicted adult height increased significantly in the deslorelin-treated patients, by 7.6 cm compared to the pretreatment baseline and by 10.3 cm compared to that in the placebo-treated patients (P < 0.005). Four of the 16 patients received concurrent GH treatment (3 among the deslorelin-treated patients and 1 among the placebo-treated patients). Omitting these patients from the analysis did not materially affect the results: predicted adult height in the deslorelin-treated patients increased by 7.2 cm compared to the pretreatment baseline and by 10.9 cm compared to that in the placebo-treated patients (P < 0.005). We conclude that pubertal delay induced by deslorelin significantly increases predicted adult height in adolescents with short stature and a normally timed puberty. Whether deslorelin treatment will increase the final height of these patients cannot be determined until they have stopped growing.

Adolescent↗
PubMed1992

Familial syndrome of endocrine and neuroectodermal abnormalities.

We report on a previously undescribed combination of endocrine and neuroectodermal abnormalities in four sibs from Burma. These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type II diabetes mellitus with elevated insulin levels, mild mental retardation, sensori-neural deafness, and alopecia without pili torti. They also had a characteristic facial appearance and fleshy hands and feet. This family appears to have a previously undescribed combination of endocrine and neuroectodermal abnormalities.

Adolescent↗
PubMed1990

Effect of thyroid hormone on epidermal growth factor-like immunoreactivity and growth velocity in cynomolgus monkeys.

To examine the potential role of epidermal growth factor (EGF) in mediating the effects of thyroid hormone on linear growth, we measured serum EGF levels by RIA in cynomolgus monkeys before and during methimazole-induced hypothyroidism, and after 9 weeks of T4 replacement at different doses. Ten castrated prepubertal monkeys were rendered hypothyroid by methimazole (0.0125% in drinking water for 12 weeks). Methimazole was continued, and T4 was then administered for 9-week intervals. Six weeks elapsed between successive T4 doses. The sequence of different T4 doses for each animal was random. Serum EGF level was measured at baseline and at the end of each treatment period with a newly developed RIA using a polyclonal antiserum against human recombinant EGF. Serum EGF level correlated significantly with the level of serum thyroxine but not with serum triiodothyronine, over the thyroxine dosage range of 1-4 micrograms/kg/day (r = 0.41, p less than 0.005). Lower-leg growth rate correlated significantly with serum EGF level over this same thyroxine dosage range (r = 0.41, p less than 0.005). These data are consistent with the hypothesis that EGF may mediate some of the effects of thyroid hormone on skeletal growth.

Animals↗
PubMed1988

The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency.

To clarify the relative usefulness of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency, we studied 54 short prepubertal children--23 with growth hormone deficiency identified by stimulation tests and 31 with idiopathic short stature who had normal responses to growth hormone stimulation. Growth hormone levels were measured in plasma samples obtained every 20 minutes for either 12 or 24 hours. The results were compared with those in 46 normal prepubertal children. Children with growth hormone deficiency had significantly lower mean 24-hour growth hormone levels (1.0 microgram per liter; range, 0.5 to 1.8) than normal children (2.8 micrograms per liter; range, 0.8 to 5.8; P less than 0.001). However, the diagnostic usefulness of the spontaneous growth hormone test was inferior to that of the stimulation tests, since it identified only 57 percent of the children with growth hormone deficiency identified by the stimulation tests. In the remaining children with growth hormone deficiency, spontaneous growth hormone levels were within the normal range. Children with idiopathic short stature had a normal mean 24-hour level of growth hormone (3.0 micrograms per liter; range, 1.1 to 6.7). No child in this group had low levels of spontaneous growth hormone secretion. We conclude that the measurement of the spontaneous secretion of growth hormone in prepubertal short children had lower sensitivity and offered no diagnostic advantage over stimulation tests. Our data do not support the routine measurement of spontaneous growth hormone secretion in the diagnosis of growth hormone deficiency.

Body Height↗
PubMed1985

Pituitary and gonadal function in the infant son of a patient with hypogonadotropic hypogonadism.

We have evaluated the pituitary-gonadal function of the infant son of a patient with hypogonadotropic hypogonadism. The father was treated with hCG and FSH to induce fertility. The son had normal external genitalia and his testicular volume increased appropriately during early infancy. Basal and post GnRH gonadotropin levels, as well as testosterone concentrations increased during early infancy. The data suggest that this infant had adequate gonadotropin secretion and testicular function. The patient illustrates the potential usefulness of evaluating the pituitary-gonadal function of male infants suspected of having hypogonadotropic hypogonadism.

Adult↗
PubMed1985

Testosterone metabolic clearance rate and production rate in the male infant rhesus monkey.

The male infant rhesus monkey (Macaca mulatta) undergoes a period of testicular activation similar to that seen in the human infant. Plasma testosterone (T) concentrations rise after birth, reaching levels of about 500 ng/dl at 1-3 mo of age and then fall to approximately 50 ng/dl at 60 mo. The plasma T metabolic clearance rates (MCRT) and production rates (PRT) were measured in two rhesus infants at 1 and 6 mo of age to determine the mechanism of the observed increase in plasma T. While there was little change in the MCRT between 1 and 6 mo, PRT was much higher at 1 mo than at 60 mo of age. These observations are consistent with the hypothesis that the increased plasma testosterone levels in infant rhesus monkeys reflect an increased production of testosterone rather than an altered metabolic disposition of the hormone.

Age Factors↗
PubMed1984

The effects of temperature on the activity of testicular steroidogenic enzymes.

Decreased sperm counts and impaired sperm motility are present in a substantial proportion of men with varicocele. Elevations in the temperature of the affected testis, and increased spermatic vein estradiol (E2) concentrations have been found in some of these patients. To investigate the possibility that increases in temperature lead to a pattern of testicular steroidogenesis that results in increased E2 synthesis, we have examined the effects of temperature changes on the activities of four important testicular steroidogenic enzymes. 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase activities were measured in the microsomal fraction of rat, pig and horse testes. Incubations were performed at 34 degrees C, 36 degrees C, and 38 degrees C. The activities of all 4 enzymes increased with each 2 degrees C temperature elevation in roughly proportional amounts. We conclude that minor elevations in incubation temperature are associated with increases in the in vitro activity of four key testicular steroidogenic enzymes.

Aldehyde-Lyases↗
PubMed1984

Isosexual precocious pseudopuberty secondary to a feminizing adrenal tumor.

We report a 2 10/12-yr-old girl with precocious pseudopuberty due to a feminizing adrenal carcinoma without Cushing's syndrome. The patient had marked elevation of plasma concentrations of the delta 5 adrenal steroids dehydroepiandosterone and dehydroepiandrosterone sulfate and increased levels of androstenedione, estrone, estradiol, and testosterone. Adrenal microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase 17-hydroxylase, 17,20-desmolase, and 21-hydroxylase activities in the tumor and adjacent normal adrenal gland were measured. The tumor had approximately normal levels of 17-hydroxylase and 17,20-desmolase activity, with low levels of 21-hydroxylase and 3 beta-hydroxysteroid dehydrogenase-isomerase activities. This combination of enzyme activity may explain the absence of Cushing's syndrome and the high levels of delta 5 adrenal steroids. This patient demonstrates that adrenal neoplasms arising in girls may mimic isosexual true precocious puberty and should be included in the differential diagnosis of precocious puberty.

Adrenal Gland Neoplasms↗
PubMed1984

The effects of sex steroids on ulnar growth during adolescence.

To investigate the relative effects of androgens and estrogens on long bone growth, we evaluated the 3-week ulnar growth velocities of 10 boys before and after the iv administration of testosterone (T; 15 mg/day), dihydrotestosterone (DHT; 7 mg/day), and estradiol (E2; 90 micrograms/day) for 4 days. Ulnar growth is a sensitive index of short term growth in children. Mean 3-week ulnar growth velocities increased from 0.49 +/- 0.11 (+/- SEM) to 1.09 +/- 0.14 mm/3 weeks after the T infusion (P less than 0.005), from 0.42 +/- 0.09 to 0.84 +/- 0.13 mm/3 weeks after the DHT infusion (P less than 0.02), and from 0.67 +/- 0.07 to 0.96 +/- 0.26 mm/3 weeks after the E2 infusion (P = NS). The mean T level was 2555 +/- 234 ng/dl during the T infusion. Mean E2 levels were 53 +/- 4 pg/ml during the T infusion and 102 +/- 7 pg/ml during the E2 infusion. Mean DHT levels were 73 +/- 7 ng/dl during the T infusion and 1115 +/- 124 ng/dl during the DHT infusion. Mean somatomedin-C levels increased to a similar degree during all infusions, but were significantly higher only during the E2 infusion (P less than 0.01). We conclude that T and DHT given for 4 days stimulated ulnar growth, while E2 at concentrations greater than those derived from T did not cause a significant increase in ulnar growth. None of the ulnar growth rates after T, DHT, or E2 treatment, however, differed significantly.

Adolescent↗
PubMed1983

Vasculitis, pulmonary cavitation, and anemia during antithyroid drug therapy.

Two thyrotoxic girls, aged 12 and 16 years, had a clinical picture consisting of purpuric skin rash, nephritis, pulmonary cavitation, hemoptysis, and profound anemia during antithyroid drug therapy. These major toxic manifestations prompted discontinuation of antithyroid drugs and institution of antibiotic and glucocorticoid therapy before the resolution of the severe illness. The girls eventually required ablative doses of radioactive iodine, and one of them had a thyroidectomy for the treatment of thyrotoxicosis. The skin biopsy specimen in one patient was indicative of mononuclear cell cutaneous vasculitis. After recovery, the patients had no evidence Of persistent anemia, nephritis, or pulmonary parenchymal disease.

Adolescent↗
PubMed1983

The effects of estradiol and progesterone on rat ovarian 17-hydroxylase and 3 beta-hydroxysteroid dehydrogenase activities.

Testosterone biosynthesis by Leydig cells can be modulated by estradiol. This modulation appears to occur at the 17-hydroxylase and 17,20-desmolase stage. In this study we have examined the effects of estradiol and progesterone on the activities of the 17-hydroxylase (17-OH) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in rat ovarian tissue, to examine the hypothesis that estradiol may regulate these enzymes in the ovary as well as in the testis. Estradiol capsule implants produced a decrease in 17-OH activity (0.5 +/- 0.05 vs. 2.1 +/- 0.1 nmol/mg protein/min, mean +/- SEM, p less than 0.001), and an increase in 3 beta-HSD activity (15.5 +/- 0.9 vs 9.7 +/- 0.7 nmol/mg protein/min p less than 0.001). Progesterone injections produced a decrease in both 17-OH (0.9 +/- 0.1 vs. 2.3 +/- 0.2 p less than 0.005) and 3 beta-HSD (2.5 +/- .4 vs. 8.6 +/- 0.5; p less than 0.005) activities. We conclude that estradiol decreases 17-OH activity in the ovary as it does in the testis. This, coupled with an increase in 3 beta-HSD may explain the pre-ovulatory increase in progesterone seen in many species. Progesterone seems to decrease the steroidogenic activity of the ovarian tissue, perhaps offering an explanation for the gonadotropin resistance seen in corpus luteus bearing ovaries.

3-Hydroxysteroid Dehydrogenases↗