PubMed Health⌕ Search

Biomedical subjects

M M Grumbach

Publications and source records attributed to M M Grumbach.

At least 73 records · Page 4Linked to original sources
PubMed1985

Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20, 22-desmolase) in a patient treated for 18 years.

Two siblings, a 9-week-old female and an 18-year-old male pseudohermaphrodite are described with deficient cholesterol side-chain cleavage activity. The female died untreated in 1954; the second sibling, a phenotypically female infant with 46 XY karyotype, was diagnosed at age 5 weeks. Massive adrenal hyperplasia was revealed by intravenous pyelography showing downward displacement of the kidneys. Secretion rates of cortisol, aldosterone, deoxycorticosterone and corticosterone were unmeasurable. Urinary 17-hydroxycorticosteroids (17-OHCS), tetrahydrocortisol, 17-ketosteroids (17-KS), pregnanetriol, pregnanediol, and delta 5-3 beta-ol steroids were not detected during prolonged administration of ACTH. Plasma concentrations and urinary excretion of gonadotrophins were increased. Gonadal mitochondria did not convert radiolabelled cholesterol to pregnenolone. The gluccocorticoid and mineralocorticoid deficiencies have been controlled well by steroid replacement therapy. Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocorticoids were given. Oestrogen replacement alone induced a pubertal growth spurt. The differential diagnosis, the effects of long-term steroid replacement therapy, and comparison with previously reported findings are discussed.

Adolescent↗
PubMed1985

Hormone ontogeny in the ovine fetus. XVIII. The effect of an opioid antagonist on luteinizing hormone secretion.

Endogenous opioid-like peptides influence gonadotropin release in adult animals and man; however, the role of these peptides in the regulation of fetal LH secretion is not known. We administered naloxone hydrochloride (1.3 mg/kg iv), a specific opioid receptor antagonist, to 22 chronically catheterized ovine fetuses of gestational ages 94-143 days (term = 147 days). As a control, each fetus also received the vehicle on a separate occasion, the sequence of the studies being randomized. After the administration of naloxone, LH secretion increased from 38.6 +/- 5.8 to 114 +/- 21 ng/h ml-1 (P less than 0.001); LH release was not affected by administration of the vehicle. Morphine (13 mg/kg) and naloxone (1.3 mg/kg) were administered together to three fetuses (gestational age 94-105 days); LH secretion was sharply reduced from 411 +/- 14.3 ng/h ml-1 after naloxone alone to 53 +/- 17.5 ng/h ml-1 after the administration of both naloxone and morphine (P less than 0.01). The response to naloxone varied with gestational age. Fetuses of 94-115 days showed a significantly higher increment in LH secretion when given naloxone (112.3 +/- 30.7 ng/h ml-1) than did older fetuses of gestational age 126-143 days (64.8 +/- 20.8 ng/h ml-1) (P less than 0.02). These findings indicate that, in the ovine fetus endogenous opioid-like peptides exert a tonic suppressive effect on LH secretion at least as early as 94 days gestation. Moreover, the effectiveness of naloxone in augmenting LH release decreases with advancing gestational age. This latter observation supports the concept that, in the ovine fetus, endogenous opioid tone is not the sole factor involved in the dampened fetal LH secretion which is characteristic of late gestation.

Animals↗
PubMed1985

Somatomedin-C levels in children and adolescents with gonadal dysgenesis: differences from age-matched normal females and effect of chronic estrogen replacement therapy.

The factors responsible for the elevation of circulating somatomedin-C/insulin-like growth factor I (Sm-C) during normal pubertal development are uncertain. To assess the role of ovarian estrogen secretion during puberty, we examined the effect of estrogen deficiency due to primary hypogonadism on Sm-C levels in late childhood and early adolescence. The concentration of immunoreactive Sm-C was measured in 36 untreated patients with gonadal dysgenesis (age, 4-16 yr); results were compared with the pattern of change in Sm-C in 153 age-matched normal girls. Between ages 4-9 yr, patients with gonadal dysgenesis had Sm-C levels similar to those in the age-matched normal subjects. In contrast to the normal girls, Sm-C levels in patients with gonadal dysgenesis did not rise after 10 yr of age and were significantly lower than those in normal girls at 11-16 yr of age. The effect of low dose estrogen therapy was assessed in eight patients with Turner's syndrome. Their Sm-C levels were measured before and during 2-12 months of treatment with ethinyl estradiol (90-220 ng/kg X day). The mean Sm-C concentration rose from 0.72 +/- 0.06 U/ml (+/- SEM) before treatment to 1.17 +/- 0.17 U/ml during estrogen treatment (P less than 0.04). In three patients who had a similar increase in Sm-C during estrogen treatment, interruption of therapy was associated with a fall in Sm-C concentrations; when estrogen therapy was reinstituted in two of these patients, Sm-C levels rose again. These results suggest that increasing endogenous estrogen production is a major determinant of the rise of circulating Sm-C that occurs during pubertal development in normal girls. Chronic estrogen deficiency, as in untreated patients with gonadal dysgenesis, is associated with failure to manifest the elevation of Sm-C that occurs during normal puberty.

Adolescent↗
PubMed1985

Treatment of true precocious puberty with a potent luteinizing hormone-releasing factor agonist: effect on growth, sexual maturation, pelvic sonography, and the hypothalamic-pituitary-gonadal axis.

We used the LHRH agonist D-Trp6-Pro6-N-ethylamide LHRH (LHRH-A) to treat 19 children (12 girls and 7 boys) with true precocious puberty. Fourteen patients had idiopathic true precocious puberty, 4 had a hamartoma of the tuber cinereum, and 1 had a hypothalamic astrocytoma. Basal gonadotropin secretion and responses to native LHRH decreased within 1 week of initiation LHRH-A therapy, and sex steroid secretion decreased within 2 weeks to or within the prepubertal range. Ultrasonographic evaluation of the uterus indicated a postmenarchal size and shape in all 11 girls studied before treatment, which reverted to prepubertal size and configuration in 5 girls during LHRH-A therapy. The enlarged ovaries decreased in size and the multiple ovarian follicular cysts regressed. Sexual characteristics ceased advancing or reverted toward the prepubertal state in all patients receiving therapy for 6-36 months. All 5 girls with menarche before therapy had no further menses. Three girls had hot flashes after LHRH-A-induced reduction of the plasma estradiol concentration. Height velocity, SDs above the mean height velocity for age, and SDs above the mean height for age decreased during LHRH-A therapy; the velocity of skeletal maturation decreased after 12 months of LHRH-A therapy and was sustained during continued therapy over 18-36 months. In 4 patients, a subnormal growth rate (less than 4.5 cm/yr) occurred during LHRH-A therapy. Six patients had cutaneous reactions of LHRH-A, but no demonstrable circulating antibodies to LHRH-A. In 2 patients in whom LHRH-A therapy was discontinued because of skin reactions, precocious sexual maturation resumed at the previous rate for the ensuing 6-12 months; subsequently, they were desensitized to LHRH-A, and during a second course of therapy, their secondary sexual development and sex steroid levels again quickly decreased. LHRH-A proved an effective and safe treatment for true precocious puberty in boys as well as girls with central precocious puberty whether of the idiopathic type or secondary to a hamartoma of the tuber cinereum or a hypothalamic neoplasm.

Age Determination by Skeleton↗
PubMed1985

Somatomedin-C in normal puberty and in true precocious puberty before and after treatment with a potent luteinizing hormone-releasing hormone agonist.

To explore further the relationship of gonadal sex steroids to the rise in somatomedin-C (Sm-C) during puberty, we studied a group of children with true precocious puberty before and after treatment which suppressed sex steroid output. Plasma estradiol and testosterone and serum acid-ethanol-extractable Sm-C were determined by specific RIAs in 7 boys and 12 girls with true precocious puberty before and at regular intervals during treatment with a potent LHRH-agonist (LHRH-A), D-Trp6-Pro9-NEt-LHRH. For comparison, Sm-C and sex steroid concentrations were determined in 266 normal adolescents and 37 normal prepubertal children, 1-9 yr of age. The mean +/- SEM Sm-C levels in normal male individuals peaked at 15 yr (2.46 +/- 0.23 U/ml) and at pubertal (genital) stage III (2.29 +/- 0.19 U/ml), and those in normal females reached their highest concentration at 12-15 yr of age and at pubertal (breast) stage III (2.47 +/- 0.15 U/ml). Sm-C concentrations correlated better with pubertal (genital or breast) stage than with chronological age for both sexes and better with testosterone levels in males than with estradiol levels in females. The mean +/- SEM Sm-C concentrations in both males and females with true precocious puberty were 2.07 +/- 0.16 U/ml before therapy and decreased significantly to 1.52 +/- 0.13 U/ml after 6 months of therapy. The mean Sm-C level of the patients remained significantly elevated for chronological age, but decreased into the normal range for bone age after 6-12 months of therapy. Sm-C correlated significantly with testosterone and estradiol levels, but not with growth rate. Mean nighttime GH secretion decreased significantly after 6 months of LHRH-A therapy. In summary, children with true precocious puberty have Sm-C elevations typical of normal puberty. The decrease in Sm-C levels after suppression of gonadal sex steroid output with LHRH-A is evidence that sex steroids are necessary to induce this elevation in Sm-C concentration. The decrease in GH secretion during LHRH-A therapy suggests that the effect of sex steroids on Sm-C levels during normal puberty is mediated, at least in part, through stimulation of GH secretion.

Adolescent↗
PubMed1985

Testicular changes in gonadotropin-independent familial male sexual precocity. Familial testotoxicosis.

A recently described form of male sexual precocity characterized by active Leydig cell differentiation and premature onset of spermatogenesis in the absence of pituitary gonadotropin stimulation has been termed familial testotoxicosis. The clinical and endocrine findings in the condition are consistent with an inherited intratesticular defect rather than central or true precocious puberty. In this report, testicular changes in biopsy specimens from a series of affected patients are presented. In all of the cases, Leydig cells demonstrated nuclear and cytoplasmic features characteristic of fully differentiated steroidogenic cells. Reinke crystals were absent. Germ cells at all stages of spermatogenesis were present, but there was evident disorganization of maturation. Spermatids exhibited a variety of structural abnormalities. Sertoli cells were characterized by complex cytoplasmic differentiation, Charcot-Böttcher crystals, and tight junction formation. The morphologic changes indicate premature differentiation of all of the major testicular cell types and are consistent with a distinctive type of intratesticular abnormality.

Child, Preschool↗
PubMed1985

Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency.

Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation.

Adolescent↗
PubMed1984

Dissociation between plasma adrenal androgens and cortisol in Cushing's disease and ectopic ACTH-producing tumour: relation to adrenarche.

To assess the effect of chronic hypersecretion of corticotropin (ACTH) and other peptides derived from proopiomelanocortin , and of cortisol, on plasma adrenal androgen concentration, plasma dehydroepiandrosterone sulphate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione (delta 4 A), and cortisol were measured in 14 children and adolescents with Cushing's disease, a 9-year-old boy with an ectopic ACTH-producing tumour, and a group of normal, age-related individuals. The plasma DHEA-S concentration was normal for chronological age in 9 of 12 patients and for bone age in 7 of 10 patients. The plasma DHEA level was normal for chronological age in 12 of 14 patients and for bone age in 8 of 10 patients. In contrast, the concentration of plasma delta 4 A was raised for chronological age in 6 of 13 patients and for bone age in 7 of 10 patients. All patients had raised plasma cortisol levels in the afternoon and other laboratory and clinical signs of hypercortisolism. In the boy with an ectopic ACTH-producing tumour, plasma DHEA-S was moderately raised, plasma DHEA was normal, and plasma delta 4 A was very high. This patient's plasma ACTH levels ranged from 1340 to 1520 pg/ml and the cortisol levels from 51 to 95 micrograms/dl. The findings suggest that a factor other than ACTH is also required for adrenal androgen secretion. Since the other proopiomelanocortin -related peptides--ie, the N-terminal peptide (1-76), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and gamma-lipotropin (gamma-LPH)--are raised in the plasma of patients with Cushing's disease, one of these is unlikely to be that putative factor.

ACTH Syndrome, Ectopic↗
PubMed1984

Treatment of Cushing's disease in childhood and adolescence by transsphenoidal microadenomectomy.

Fifteen unselected children and adolescents with Cushing's disease were treated by transsphenoidal exploration and microadenomectomy. In only three patients was radiographic examination of the sella turcica, including computed tomography, useful in indicating the presence and location of a pituitary microadenoma. Transsphenoidal microadenomectomy corrected hypercortisolism in 14 of the 15 patients; no adenoma was detected in one patient, and one required a second operation six months after the first because of incomplete removal of the adenoma. All 14 lost weight and cushingoid stigmata and had normal or catch-up growth (if epiphyses were not fused) and progression of puberty. In one patient, a recurrence was successfully treated by repeat microadenomectomy six years after the first procedure. The low morbidity and failure rate of the procedure, the low recurrence rate, the rapid amelioration of signs of hypercortisolism, and the preservation of pituitary function in the present study support transsphenoidal microadenomectomy as a low-risk approach to the initial treatment of Cushing's disease in childhood and adolescence.

Adenoma↗
PubMed1984

Hormone ontogeny in the ovine fetus. XVII. Demonstration of pulsatile luteinizing hormone secretion by the fetal pituitary gland.

To determine whether pulsatile gonadotropin secretion occurs in the fetus, plasma immunoreactive ovine LH (oLH) concentrations were determined by homologous RIA in serial samples obtained in 51 chronically catheterized fetuses between 79 and 140 days gestation. Pulsatile secretion of LH was detected in 39 fetuses, with a peak amplitude ranging from 1.2-11.5 ng/ml (mean +/- SD, 4.5 +/- 2.3 ng/ml). The mean plasma oLH concentration between pulses was 0.4 +/- 0.23 ng/ml. The mean amplitudes of the LH pulses were similar in the age range studied, and a sex difference was not detected. The estimated interpulse interval (determined by dividing the total number of hours during which blood samples were obtained by the number of pulses demonstrated) was 2.4 h between 91 and 110 days gestation. The pattern of plasma oFSH concentration was examined in 20 fetuses between 98 and 123 days gestation. Six fetuses with gestational ages between 106 and 115 days had FSH pulses that were equal or more than 2 times the sensitivity of the RIA. This study demonstrates a pulsatile mode of LH secretion by the ovine fetal pituitary as early as 81 days gestation and provides indirect evidence for pulsatile LRF secretion by the fetal hypothalamus and an operative LRF pulse generator by midgestation, the earliest stage in gestation studied.

Animals↗
PubMed1984

Effect of growth hormone (GH)-releasing hormone (GRH) on plasma GH in relation to magnitude and duration of GH deficiency in 26 children and adults with isolated GH deficiency or multiple pituitary hormone deficiencies: evidence for hypothalamic GRH deficiency.

Synthetic, amidated, 44 amino acid GH-releasing hormone ( GRH -44) was administered iv at a dose of 5 micrograms/kg to 20 patients with severe GH deficiency (GHD), 6 children and adolescents with partial GHD, and 6 non-GH deficient ( NGHD ) children and adolescents. The 17 patients with severe GHD that responded to GRH -44 had lower peak concentrations of plasma GH than the NGHD individuals (5.0 +/- 1.2 (SEM) vs. 27.2 +/- 3.5 ng/ml; P less than 0.0001). The children and adolescents with severe GHD tended to have higher peak GH responses to GRH -44 than the GHD adults (6.9 +/- 1.7 vs. 2.4 +/- 0.3 ng/ml) although the difference was not significant. The peak GH concentration was attained earlier in the GHD children and adolescents than in the GHD adults (28 +/- 4.7 vs. 69.3 +/- 13 min, P less than 0.004). There was a negative correlation between chronological age and peak plasma GH response to GRH in the children and adolescents with severe GHD (r = -0.758, P less than 0.02). Children and adolescents with partial GHD had a higher mean peak concentration of plasma GH (13. 1 +/- 1.8 ng/ml) than the children, adolescents, and adults with severe GHD (P less than 0.04), but one lower than the NGHD children and adolescents (P less than 0.05). In both severe and partial GHD the GH response to GRH was greater than that elicited by standard pharmacological tests. Serum somatomedin-C did not increase after a single pulse of GRH -44 in the 12 GHD patients studied. PRL increased minimally 30 min after 5 micrograms/kg iv GRH -44 in patients with multiple hypothalamic-pituitary hormone deficiencies but not in patients with isolated GHD or in NGHD individuals. The GH responses to GRH suggest that the majority of patients with isolated GHD as well as those with multiple hypothalamic-pituitary hormone deficiencies have deficiency of hypothalamic GRH . Lack of a GH response to a single pulse of GRH does not exclude GRH deficiency as priming of the somatotrope with multiple pulses of GRH may be necessary to rule out a hypothalamic defect in the nonresponders. The results of this study support the potential usefulness of GRH or its analogs in the diagnosis and treatment of selected patients with disorders of GH secretion.

Adolescent↗
PubMed1983

Growth hormone treatment for short stature.

Fifteen short but otherwise normal children, 4.3 to 15.5 years old, with heights greater than 3 S.D. below the mean value for age, growth rates less than or equal to 5.0 cm per year, and normal serum levels of immunoreactive growth hormone in response to provocative stimuli (peak greater than or equal to 10 ng per milliliter) were treated with intramuscular injections of pituitary growth hormone (0.1 U per kilogram) three times weekly for six months, as were 14 children with documented growth hormone deficiency. In all the latter children growth rate increased by more tan 2.0 cm per year during treatment. In 6 of the 14 short normal children who remained prepubertal, growth rate also increased, by 2.2 to 4.2 cm per year during treatment; four of these children had normal base-line serum somatomedin C concentrations. In both short normal children and children with growth hormone deficiency, the increment in serum somatomedin C concentrations after 4 or 10 daily injections of growth hormone correlated with bone age but not with later growth or growth hormone levels. Among the short normal children, those who responded to growth hormone were younger and had a greater delay in bone age and a slower pretreatment growth rate than the nonresponders. These observations suggest that a dose of growth hormone comparable to that used for the treatment of hypopituitarism increases growth rate in some short normal children.

Adolescent↗
PubMed1983

Hormone ontogeny in the ovine fetus: XIV. The effect of 17 beta-estradiol infusion on fetal plasma gonadotropins and prolactin and the maturation of sex steroid-dependent negative feedback.

17 beta-Estradiol (E2; 100 micrograms/kg X day) was infused iv for 6 days into three chronically catheterized ovine fetuses beginning at 105-106 days of gestation (term, 147 days) and into four younger fetuses for 3 days commencing at 87-92 days. Control studies were performed on three fetuses at each age. At 90 days, E2 had no effect on the basal concentration of either LH or FSH. In both control and E2-infused fetuses, repeated LHRH testing was associated with a decreased LH response, but the decrease was not greater in the E2-infused fetuses. The FSH response was unaffected in either group. At 105 days, E2 caused suppression of the mean basal concentration of plasma LH from 1.2 +/- 0.1 to 0.1 +/- 0.1 ng/ml (P less than 0.01) and of basal FSH from 5.6 +/- 0.5 to 3.3 +/- 0.6 ng/ml (P less than 0.05). The LH response to LHRH administration (50-micrograms iv bolus) also was suppressed by E2. The maximal incremental LH response fell from 7.1 +/- 0.4 to 3.3 +/- 0.5 ng/ml (P less than 0.01); the integrated response decreased from 5.8 +/- 0.2 to 1.8 +/- 0.2 ng/ml X h (P less than 0.01). However, no effect was observed on the rise in FSH concentration evoked by LHRH. In control studies at 105 days, basal and LHRH-stimulated gonadotropin concentrations remained constant during the experiment. These results indicate that the capacity for exogenous E2 to suppress fetal pituitary gonadotropin secretion in the ovine fetus develops between 90 and 105 days of gestation, before the normal ontogenic decrease both in the basal concentration of fetal pituitary gonadotropins and in LHRH-stimulated FSH and LH secretion, which occur later in gestation. We suggest that the development of the E2-sensitive negative feedback mechanism in the fetal hypothalamic-pituitary unit is a major factor in this decrease. At 90 days gestational age, the mean fetal plasma concentration of PRL was not affected by the infusion of E2 into the fetus (5.9 +/- 1.5 ng/ml before E2 infusion 8.1 +/- 3.2 ng/ml during E2 infusion). However, at 105 days, the mean PRL concentration rose from 49.3 +/- 18.2 to 101.6 +/- 26.1 ng/ml (P less than 0.01) after the infusion of E2. The capacity for E2 to stimulate PRL release develops in parallel with the rise in fetal plasma PRL and estrogen concentrations. The results provide evidence that circulating estrogens are a determinant of fetal PRL concentrations in late gestation.

Animals↗
PubMed1983

Hormone ontogeny in the ovine fetus. XV. Studies of adenohypophysial hormones after fetal pituitary stalk section: evidence for an extrahypothalamic dopaminergic influence on fetal prolactin secretion.

The administration of a dopamine antagonist, haloperidol, to the ovine fetus in late gestation elevates plasma concentrations of PRL, suggesting tonic dopaminergic inhibition of fetal PRL secretion. The source of this dopaminergic inhibition was investigated in chronically catheterized ovine fetuses (104-135 days of gestation) after hypophysial stalk section (SS; n = 4) and in sham-operated controls (CON; n = 7). Basal PRL levels were similar in the two groups of fetuses. After the administration of TRF (250 micrograms, iv), PRL levels rose comparably in both the SS and CON fetuses. The only difference was a higher mean incremental response (P less than 0.02) in the SS fetuses. The dopamine agonist apomorphine (100 micrograms/kg, iv) induced a similar suppression of fetal PRL concentrations in CON (n = 4) and SS (n = 2) fetuses. After the administration of haloperidol (1 mg, iv) to the CON fetuses (n = 7), the concentration of fetal PRL rose (P less than 0.01). In the SS fetus (n = 4), haloperidol induced a rise in PRL concentrations (P less than 0.01); however, the response to haloperidol was less (P less than 0.01) in SS than in CON fetuses. These data suggest that there is persistent dopaminergic inhibition of PRL secretion in the fetus after complete stalk section, and that the source of this dopamine is extrahypothalamic. The greater incremental PRL response to TRH and the lesser response to haloperidol in the SS fetus than in CON are evidence for a hypothalamic component to the dopaminergic inhibition in the intact fetus. Basal FSH concentrations and the gonadotropin response to LRF were not affected by stalk section in fetuses studied 5-8 days after surgery. Both the PRL and the GH responses to 5-hydroxytryptophan were abolished by stalk section. After stalk section GH levels fell, however, significant concentrations of GH were measurable in fetal plasma in late gestation, which suggests that the fetal pituitary can secrete GH in the absence of hypothalamic stimulation at this stage in gestation.

Animals↗
PubMed1983

Hormone ontogeny in the ovine fetus. XVI. Plasma immunoreactive somatomedin C/insulin-like growth factor I in the fetal and neonatal lamb and in the pregnant ewe.

The basic somatomedins [SMC/insulin-like growth factor I (IGF-I)] and the neutral somatomedins (multiplication-stimulating activity/IGF-II) exhibit different patterns during pregnancy and ontogeny. We have adapted a specific RIA for SMC/IGF-I to study the pattern of change of this growth factor in fetal, neonatal, and adult sheep plasma. Acid-ethanol extraction of the samples was performed to minimize the interference of the somatomedin-binding proteins in the RIA. Results are expressed in terms of a neonatal lamb reference plasma with an arbitrarily assigned potency of 1 U/ml (equivalent to 500 ng/ml purified human IGF-I). In chronically catheterized fetal and neonatal lambs, plasma SMC/IGF-I rose from 0.14 +/- 0.02 U/ml before 100 days of gestational age (term 147 days) to 0.22 +/- 0.01 U/ml between 101 and 144 days. In neonates (1-33 days), the mean plasma concentration of SMC/IGF-I was 0.93 +/- 0.07 U/ml. In adult sheep, plasma SMC/IGF-I was twice as high in rams as in nonpregnant ewes (0.88 +/- 0.06 vs. 0.44 +/- 0.03 U/ml); in pregnant ewes plasma SMC/IGF-I did not change significantly between the second and the last third of gestation and was always higher than the fetal levels. The rise in fetal plasma SMC/IGF-I around 100 days of gestation parallels the rise in fetal GH and PRL concentrations. The discrepancy between the present results and earlier reports based on bioassays and radioreceptor assays may be due to the presence of high circulating concentrations of IGF-II-like peptides in the ovine fetus. The striking sex difference in the plasma concentrations of SMC/IGF-I in adult sheep suggests that SMC/IGF-I generation or disposition is influenced by sex steroids.

Animals↗
PubMed1983

The induction of antibodies to human luteinizing hormone by contaminated clinical pituitary hormone preparations.

Three children with hypopituitarism had elevated LH levels measured by RIA which were incompatible with their stage of sexual maturation. Each of the children had been administered parenteral pituitary hormone preparations: one patient, human (h) GH for 3 2/1 yr; one patient, bovine TSH twice to evaluate thyroid responsiveness; and two patients, posterior pituitary extract by nasal insufflation for 7 5/12 ad 4 9/12 yr to treat diabetes insipidus. Each of these children had developed antibodies of the immunoglobulin G class which bound [125I]hLH in vitro in a displaceable fashion. In two of the patients, the antibody reacting with hLH was found after therapy with pituitary hormones of bovine or porcine origin and before treatment with hGH, while on child had received only hGH therapy. These antibodies interfered in the assay for hLH and were responsible for the spurious elevations of serum immunoreactive hLH. None of these children had undergone spontaneous puberty, including at least one who may not have been gonadotropin deficient. To reduce the risk of generating high potency neutralizing antibodies, only highly purified, monomeric pituitary hormone preparations or pure synthetic hormone preparations should be used for diagnosis and chronic replacement therapy.

Adolescent↗