Pituitary Growth Hormone Content Research Articles

Functional Interrelationships Between Adrenergic and Opioid Systems in the Neuroregulation of Growth Hormone Secretion in Infant Rats

Abstract Functional interrelationships between hypothalamic adrenergic and opioid systems were studied in 10-day-old male and female rats. Either clonidine (150 mug/kg, sc), an alpha(2)-adrenoceptor agonist, or FK 33-824 (1 mg/kg, sc), a synthetic analog of met-enkephalin, increased plasma growth hormone (GH) levels, the increment being significantly higher with FK 33-824 than with clonidine. Pharmacologic blockade of opioid receptors with naloxone (5 mg/kg, sc) did not modify either basal GH levels, or the GH response to clonidine, whereas blockade of alpha(2)-adrenoceptors with yohimbine (2.5 mg/kg, sc) reduced basal GH levels and partially counteracted the FK 33-824-induced GH rise. Clonidine (150mu/kg, sc, twice daily) administered from postnatal day 5 to 9, increased basal GH levels and pituitary GH content. In these pups, acute administration of clonidine failed to further release GH, but the GH response to acute administration of FK 33-824 was significantly enhanced. A 5-day treatment with FK 33-824 (1 mg/kg, sc, twice daily), neither modified basal GH levels, nor pituitary GH content. Under these conditions, the in vivo GH response to an FK 33-824 challenge was significantly enhanced, and the response to clonidine was preserved. Pituitaries from FK 33-824-pretreated rats were hyperresponsive to GH-releasing hormone (10(-7) M). In summary, our data indicate that in rat pups: 1) two separate components i.e. one adrenergic, the other extra-adrenergic, subserve the GH-releasing effect of opioid peptides; 2) in contrast to short-term stimulation of alpha(2)-adrenoceptors, stimulation of opioid receptors does not trigger GH synthesis or induce down-regulation or tolerance; 3) short-term opioid stimulation does not affect an alpha(2)-adrenergic challenge, but sensitizes to an opioid challenge.

Growth hormone and insulin-like growth factor-I measurements in high growth (hg) mice

Effects of a recessive gene causing high growth (hg) were studied on two major components of the growth axis in mice. Plasma and pituitary levels of growth hormone and plasma levels of insulin-like growth factor I (IGF-I) were measured in three lines homozygous for hg, each compared with a control line of alike genetic background but wild type for the hg locus (Hg). Line Gh (hghg) and line GH (HgHg) are from a line which had undergone long-term selection for high postweaning weight gain; line Ch (hghg) and line CH (HgHg) were extracted from the second backcross of Gh to C57BL/6J; line L54 (hghg) was from the sixth backcross to C57BL/6J (B6) (HgHg). Pituitary GH levels and plasma IGF-I levels were measured in both sexes at 3, 4.5, 6 and 9 wk of age. Plasma growth hormone was measured in 8- to 12-wk-old males at hourly intervals from 08.00 to 17.00. Body weight in lines homozygous for hg at 6 and 9 wk of age was 10-30% greater than in control lines. The ontogeny of this increased growth depended on genetic background. Pituitary growth hormone content was 52% lower in the two hghg lines measured (lines Ch and Gh) than in control lines at 4.5, 6 and 9 wk. Plasma growth hormone levels were also much lower in hg mice, with values only 20-30% of those in their respective controls. hg lines showed consistently low plasma growth hormone levels throughout the 9 hr sampling period, while control lines expressed the characteristic pulsatile hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Homologous radioimmunoassay for bullfrog growth hormone

Antiserum against bullfrog growth hormone (fGH) was produced by immunizing rabbits with the highly purified fGH obtained from adenohypophyses of adult bullfrogs. Histological studies on bullfrog adenohypophyses revealed that the cells that immunologically reacted with the antiserum against fGH corresponded to the ones positively stained with the antiserum against rat GH. The antiserum together with fGH and 125I-fGH was employed to develop a radioimmunoassay (RIA) for fGH. Several dilutions of plasma and of pituitary homogenate of both adult and larval bullfrogs yielded dose-response curves which were parallel to the standard curve. Ovine prolactin (PRL) and growth hormone (GH); eel and salmon GHs; and bullfrog LH, FSH, TSH, PRL, and neurointermediate lobe homogenate did not react in this assay. Plasma from hypophysectomized bullfrogs had no detectable immunoreactive GH. Pituitary homogenates of Bufo japonicus, Xenopus laevis, and Cynops pyrrhogaster gave inhibition curves which did not parallel the standard. The homologous RIA for bullfrog GH thus developed was applied for the determination of plasma and pituitary GH levels in the larvae and adults. Plasma GH levels were relatively low during preclimax period and rose as metamorphosis progressed. Plasma GH concentrations were maximum in the juvenile frogs and decreased as the animals grew up. Pituitary GH concentrations also increased as metamorphosis progressed. After metamorphosis, pituitary GH concentrations declined as the frogs gained weight. There was no sex difference in plasma and pituitary GH levels in the adult.

Neonatal Treatment with Monosodium Glutamate: Effects of Prolonged Growth Hormone (GH)-Releasing Hormone Deficiency on Pulsatile GH Secretion and Growth in Female Rats*

Administration of monosodium glutamate (MSG) to neonatal rodents produces permanent lesions of hypothalamic arcuate neurons that secrete GH-releasing hormone (GHRH). The present study was intended to determine the consequences of GHRH deficiency on the pulsatile GH secretory pattern and growth in MSG-treated female rats and to compare these effects with those observed in male littermates. Male and female rats were injected with MSG [4 mg/g body wt (BW), sc] or saline (controls) on days 2, 4, 6, 8, and 10 after birth. Immunoreactive GHRH concentrations were decreased in the hypothalamus (by 60%) and in the median eminence (by 95%) of adult male and female MSG-treated rats. In contrast, somatostatin concentrations were unaffected. BW and linear growth were severely impaired in male MSG-treated rats, but in MSG-lesioned females BW was not different from controls, and the attenuation of longitudinal growth was less severe and the obesity more pronounced than in males. These sex differences occurred despite similar reductions (by 55%) in serum insulin-like growth factor I concentrations in male and female MSG-treated rats. MSG treatment also produced decreases in pituitary wt and GH content (by 60%), independent of sex. Pulsatile GH secretion was studied by serial blood sampling of chronically cannulated, freely moving rats. Plasma GH patterns were analyzed by the PULSAR program. Compared to controls, treatment with MSG led to a marked inhibition (by 90%) of GH secretion in both sexes. Significant reductions in GH pulse amplitude (-95%) and pulse duration (-62%) were observed in males, whereas pulse amplitude (-85%), pulse frequency (-67%), and baseline GH concentrations (-80%) were markedly reduced in females. The GH responses to an iv bolus injection of rat GHRH (1 microgram/rat) was severely blunted in both male and female MSG-treated rats. This study demonstrates that GHRH deficiency in female rats results in a marked inhibition of GH pulses, as in males, but also causes severe and sex-specific reductions in GH basal secretion and pulse frequency. These observations suggest that hypothalamic GHRH secretion in female rats is more continuous than in males and is a determinant of the elevated interpulse secretion of GH. Moreover, body wt and linear growth are less severely affected by arcuate lesions in female animals, compared to males. These sex-related differences in growth rates may result in part from the tendency of female MSG-lesioned rats to become more obese than males, and the development of obesity, in turn, may antagonize the factors that tend to slow linear growth.(ABSTRACT TRUNCATED AT 400 WORDS)

Ovarian Role in the Modulation of Pituitary Responsiveness to Growth Hormone-Releasing Hormone in Rats

The influence of ovarian function on the pituitary responsiveness to growth hormone-releasing hormone (GHRH) was studied by measuring GH levels in serum before and after the injection of GHRH 1-29 NH2 (5 micrograms/kg i.v.) in female Wistar rats under sodium pentobarbital anesthesia (50 mg/kg i.p.). In the first experiment, GHRH was administered to 90-day-old females in different phases of the estrous cycle (in the morning and afternoon of proestrus and in the morning of estrus, diestrus 1 and diestrus 2). In the second experiment, females were ovariectomized or sham-operated on day 23 and analyzed on days 30, 45, 60 and 90. Pituitary growth hormone (GH) content in females ovariectomized or sham-operated on day 23 was also analyzed at different ages. In the third experiment, females ovariectomized or sham-operated on day 83 were tested on day 90. Results showed that (a) pituitary responsiveness to GHRH changes throughout the estrous cycle is maximal in diestrus and minimal in proestrus; (b) GHRH stimulated GH secretion in intact and ovariectomized females on days 45, 60 and 90, but not on day 30; (c) the age increase of GH responsiveness to GHRH administration was slightly reduced in animals ovariectomized on day 23; (e) the age increase of pituitary GH content was similar in control and ovariectomized females; and (d) ovariectomy on day 83 reduced pituitary responsiveness to GHRH more effectively than ovariectomy on day 23.(ABSTRACT TRUNCATED AT 250 WORDS)

Robust Growth Hormone (GH) secretion in aged female rats co-administered GH-releasing hexapeptide (GHRP-6) and GH-releasing hormone (GHRH)

Aging is associated with a blunted growth hormone (GH) secretory response to GH-releasing hormone (GHRH), in vivo. The objective of the present study was to assess the effects of aging on the GH secretory response to GH-releasing hexapeptide (GHRP-6), a synthetic GH secretagogue. GHRP-6 (30 μg/kg) was administered alone or in combination with GHRH (2 μg/kg) to anesthetized female Fischer 344 rats, 3 or 19 months of age. The peptides were co-administered to determine the effect of aging upon the potentiating effect of GHRP-6 on GHRH activity. The increase in plasma GH as a function of time following administration of GHRP-6 was lower (p < 0.001) in old rats than in young rats; whereas the increase in plasma GH secretion as a function of time following co-administration of GHRP-6 and GHRH was higher (p < 0.001) in old rats than in young rats (mean Cmax = 8539 ± 790.6 μg/1 vs. 2970 ± 866 μg/1, respectively; p <0.01). Since pituitary GH concentrations in old rats were lower than in young rats (257.0 ± 59.8 μg/mg wet wt. vs. 639.7 ± 149.2 μg/mg wet wt., respectively; p < 0.03), the results suggested that GH functional reserve in old female rats was not linked to pituitary GH concentration. The differential responses of old rats to individually administered and co-administered GHRP-6 are important because they demonstrate that robust and immediate GH secretion can occur in old rats that are appropriately stimulated. The data further suggest that the cellular processes subserving GH secretion are intact in old rats, and that age-related decrements in GH secretion result from inadequate stimulation, rather than to maladaptive changes in the mechanism of GH release.

Growth hormone (GH) secretion in the dwarf rat: release, clearance and responsiveness to GH-releasing factor and somatostatin

The new mutant GH-deficient dwarf (Dw) rat was used to study the effects of GH-releasing factor (GRF) or somatostatin (SRIF) on GH release. In anaesthetized adult Dw female rats, i.v. injections of GRF (0.031-2.0 micrograms) elicited a dose-dependent release of GH. Although the peak plasma GH responses to maximal GRF doses were much lower in adult Dw rats compared with normal rats of this strain (AS), the responses largely reflected their relative pituitary GH contents (140 +/- 17 micrograms vs 2.9 +/- 0.4 micrograms, AS vs Dw (means +/- S.E.M.), P less than 0.001). Except at 20 days of age, normal AS rats were more sensitive to GRF than Dw rats despite their larger body weight. Peak GH responses to injection of 31.25 ng GRF increased nine-fold in normal rats between 20 and 40 days, whereas the GH responses to this GRF dose diminished in Dw rats over this age range, and their pituitary GH content was only 2-5% of that of age-matched AS rats. Treatment with human GH (200 micrograms/day for 7 days) stimulated growth in 40-day-old Dw rats and slightly increased the GH response to a low dose of GRF. Basal GH levels in adult Dw animals were sevenfold lower than in AS rats (2.4 +/- 0.3 vs 17.6 +/- 3.3 micrograms/l P less than 0.001) and were further suppressed by i.v. infusion of SRIF (25 micrograms/h). As in normal rats, a rebound GH secretion occurred in Dw rats after stopping SRIF, which was blocked by injection of anti-GRF serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Thyroid Hormone Deficiency and Replacement on Rat Hypothalamic Growth Hormone (GH)-Releasing Hormone Gene Expressionin VivoAre Mediated by GH

The role of thyroid hormone and GH in the regulation of hypothalamic GH-releasing hormone (GRH) gene expression in the rat was examined after the induction of thyroid hormone deficiency by thyroidectomy. Thyroidectomy resulted in a time-dependent decrease in hypothalamic GRH content, which was significant by 2 weeks postoperatively, and a reduction in pituitary GH content to 1% of the control level by 4 weeks. In contrast, GRH secretion by incubated hypothalami under both basal and K(+)-stimulated conditions was increased after thyroidectomy. Hypothalamic GRH mRNA levels also exhibited a time-dependent increase, which was significant at 1 week and maximal by 2 weeks after thyroidectomy. Administration of antirat GH serum to thyroidectomized rats resulted in a further increase in GRH mRNA levels. T4 treatment of thyroidectomized rats for 5 days, which also partially restored pituitary GH content, lowered the elevated GRH mRNA levels. However, comparable effects on GRH mRNA levels were observed by rat GH treatment alone. These results suggest that the changes in hypothalamic GRH gene expression after thyroidectomy in the rat are due to the GH deficiency caused by thyroidectomy, rather than a direct effect of thyroid hormone on the hypothalamus, since the changes were reversible by GH alone despite persistent thyroid hormone deficiency. In addition, they further support the role of GH as a physiological negative feedback regulator of GRH gene expression.

Dynamic of the GRF-induced GH response in genetically obese Zucker rats: influence of central and peripheral factors

To determine the time onset of the growth hormone (GH) alteration in the genetically obese rat, we studied the in vivo and in vitro rat growth hormone releasing factor (rGRF(1–29)NH 2)-induced GH secretion in 6- and 8-week-old lean and obese male Zucker rats. Under sodium pentobarbital anesthesia, rGRF(1–29)NH 2 (GRF) was injected intravenously at two doses: 0.8 and 4.0 μg/kg b.w. Basal serum GH concentrations were similar in lean and obese age-matched animals. The GH response to both GRF doses tested was unchanged in 6-week-old obese rats as compared to their lean litter mates. In contrast, a significant decrease of the GH secretion in response to 4.0 μg/kg b.w. GRF was observed in the 8-week-old obese rats. The effect of GRF (1.56, 6.25 and 12.5 pM) was further studied in vitro, in a perifusion system of freshly dispersed anterior pituitary cells of lean and obese Zucker rats. Basal GH release was similar in the 6-week-old animal group. In contrast, it was significantly decreased in 8-week-old obese rats as compared to their lean litter mates. Stimulated GH response to 1.56 and 6.25 pM GRF was significantly greater in the 6-week-old obese group than in the age-matched control group. In contrast, the GH response to all GRF concentrations tested was significantly decreased in the 8-week-old obese rats as compared to their respective lean siblings. In 8-week-old obese rats, a decrease of GH pituitary content and an increase of hypothalamic somatostatin (SRIF) concentration were observed. Insulin and free fatty acid serum were significantly increased in 8-week-old obese rats. In contrast, lower insulin-like growth factor I serum levels were observed in the obese animals as compared to their lean litter mates. Finally, to further clarify the role of the periphery in the inhibiton of GH secretion observed in the 8-week-old fatty rats, we exposed cultured pituitary cells of 8-week-old lean animals to 17% serum of their obese litter mates. A significant decrease of GRF-stimulated GH secretion of lean rat pituitary cells exposed to the obese serum was noted ( P < 0.05). This study demonstrates that, in the obese Zucker rat, an alteration of the GH response to GRF is evident by the 8th week of life. This defective GH secretion could be related to peripheral and central abnormalities.

Depletion of Hypothalamic Growth Hormone-Releasing Hormone by Neonatal Monosodium Glutamate Treatment Reveals an Inhibitory Effect of Betamethasone on Growth Hormone Secretion in Adult Rats

Rats were treated with monosodium glutamate (MSG), 4 mg/g on alternate days for the first 10 days of life, to induce lesions of the arcuate nucleus and destroy the majority of growth hormone-releasing hormone (GHRH) neurones. At 10 weeks of age, control (n = 42) and MSG-treated (n = 36) male rats were used to test the effect of glucocorticoids on growth hormone (GH) secretion. Each treatment group was divided into six study groups to determine the effect of betamethasone (BM), administered either 3 or 20 h prior to sacrifice, alone and in combination with hypoglycaemia (insulin 0.1 U/100 g). BM treatment of male rats was without effect on plasma GH levels in control animals. In contrast, glucocorticoid administered either 3 h before sacrifice or the previous evening significantly reduced circulating GH (p less than 0.001) in MSG-treated animals. The difference in plasma GH response to BM pretreatment in control rats and those with lesions of the arcuate nucleus indicates a hypothalamic action of glucocorticoids, presumably on somatostatin and GHRH neurones. In control animals the effects appear to be counterbalancing, but following destruction of GHRH neurones an uncompensated inhibitory influence was observed. Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls. Female rats which had undergone the same neonatal MSG treatment (n = 40) when sacrificed 1 week after their male counterparts showed similar reductions in body weight (-15%), hypothalamic GHRH (-74%), and pituitary GH (-67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in Growth Hormone Secretion in Spontaneously Hypertensive Rats

Secretion of the growth hormone (GH) in spontaneously hypertensive (SH) male rats has been determined and compared with that of normotensive Wistar-Kyoto (WKY) controls. In a first set of experiments, plasma GH concentration and pituitary GH content were measured in SH rats 30, 60 and 90 days old. 30-day rats showed reduced GH plasma and pituitary levels, whereas in 60- and 90-day-old rat no differences in GH plasma concentration and increased GH pituitary content were observed. In a second set of experiments, 90-day-old SH male rats anesthetized with sodium pentobarbital and intravenously injected with growth hormone-releasing factor (GRF) showed an amplitude and duration of response to injected hormone higher than WKY controls. In a third set of experiments, hemipituitaries of 90-day-old SH males were incubated for 2 h in Krebs-Ringer-bicarbonate either in the presence or in the absence of GRF. In the absence of GRF stimulation, the in vitro release of GH was higher than in WKY controls, whereas in the presence of GRF the sensitivity and the maximum response to GRF was reduced in comparison with normotensive male rats. These results indicate that SH rats have decreased pituitary content and plasma GH concentration before puberty. Besides, they showed increased pituitary GH content in adulthood and opposite changes in the in vivo and in vitro response to GRF.

Delay of puberty and impairment of growth in female rats given a non competitive antagonist of NMDA receptors

Reportedly, excitatory amino acids are involved in the control of gonadotropin secretion of rats and non-human primates. The aim of this study was to investigate the effect of chronic blockade of NMDA (N-methyl-D-aspartic acid) receptors by the non competitive receptor antagonist MK-801 on gonadotropin secretion and the onset of puberty in female rats. Moreover, since in humans alterations of the timing of puberty frequently coexist with disturbances of body growth, suggesting a common etiology for both events, we evaluated the effect of MK-801 also on the neural mechanisms controlling growth hormone (GH) secretion. Twenty-one-day-old female rats were treated with MK-801 (0.2 mg/kg ip, bid) or placebo for 10 days and were killed after 7 days of withdrawal. Administration of MK-801 induced a significant impairment of growth rate without altering food intake, and a delay in vaginal opening. Pituitaries from rats treated with MK-801 had a reduced luteinizing hormone (LH) content, and secreted in vitro lower amounts of LH both under basal and LHRH-stimulated conditions. MK-801 treated rats had a lower pituitary GH content and basal and GHRH-stimulated GH release and reduced plasma insulin-like growth factor-I levels. These data indicate that blockade of NMDA receptors in a critical period of the female rat life-span: 1) delays puberty by reducing gonadotropin secretion; 2) impairs growth rate by reducing GH secretion, with a mechanism still to be clarified.

The ontogeny of growth hormone in the human fetal pituitary

To examine the ontogeny of growth hormone synthesis and secretion in human fetus, growth hormone messenger ribonucleic acid was measured in 11 pituitaries from fetuses of 16 to 27 weeks of gestation by hybridization of cytosol ribonucleic acid with complementary deoxyribonucleic acid labeled with phosphate 32. Pituitary growth hormone content and serum growth hormone, thyroxine, and cortisol concentrations were assessed by radioimmunoassay. Growth hormone messenger ribonucleic acid content in the fetal pituitary increased from the early midtrimester, reaching a level 15.3 times higher at 27 weeks of gestation than the value at 16 weeks. However, growth hormone content in the pituitary showed no evident change during 16 to 21 weeks of gestation and started to increase after 22 weeks. Serum concentration of growth hormone was variable but always >50 ng/ml, and the maximal level was observed at 20 weeks of gestation (141 ng/ml). Although serum thyroxine concentration in the fetuses showed no correlation with pituitary growth hormone content or serum growth hormone concentration, serum concentration of cortisol was correlated positively with growth hormone content in the fetal pituitary. These results suggest that the maturation of the growth hormone synthesis and secretion system in the fetal pituitary occurs after 22 weeks of gestation and that cortisol may play some role in the ontogenesis of growth hormone. (AM J OBSTET GVNECOl 1989;160:729-33.)

Growth Hormone (GH) Deprivation Induced by Passive Immunization against Rat GH-Releasing Factor Delays Sexual Maturation in the Male Rat*

GH deprivation after passive immunization against rat GRF (rGRF) markedly affects somatic growth in male rats. Since it has been postulated that GH and probably insulin-like growth factor-I (IGF-I) might have a permissive role on sexual maturation, the effects of GH deprivation on the course of sexual maturation were tested. Male rats were treated with a potent anti-rGRF serum between 15 and 39 days of life (0.25 ml administered sc every second day). Body weight of treated rats averaged 62% of that of control (normal rabbit serum-treated) rats at 40 days of life (d), and 64% at 50 d after which age, treated rats started to grow normally. At 40 and 50 d, pituitary GH content was very much depressed (representing approximately 20% of control values at both ages), plasma GH was undetectable, and plasma IGF-I levels averaged 30% of those of control rats. At 70 d, 30 days after cessation of treatment, pituitary GH content, and IGF-I secretion were almost normal. At 40 d, testes and seminal vesicles of treated rats were small-for-age in agreement with significantly decreased plasma levels of FSH and delayed spermatogenesis characterized by the presence of only few or no spermatozoa. At 50 d, 10 days after cessation of anti-rGRF injections, progress of sexual maturation was found to be consistent with age and coincided with normalization of growth rate. At 40 and 50 d, pituitary contents of FSH and LH were severely decreased but became normal at 70 d. In conclusion, GH deprivation which markedly affected somatic growth induced a transient delay of sexual maturation. GH deficiency seems to have affected mostly the synthesis and secretion of FSH, thus producing a delay in testes growth and in the differentiation of the germinal cells. The low levels of IGF-I might also have been the cause for the delay of maturation at the pituitary and/or the gonadal levels.

Interactions between growth hormone-releasing hormone and glucocorticoids in male rats

While chronic glucocorticoid treatment increases pituitary growth hormone (GH) content in rats and primates and increases pituitary GH release in response to growth hormone-releasing hormone (GHRH) in rats, it also inhibits somatic growth. We investigated these opposite actions in rats using the synthetic glucocorticoid dexamethasone. Seven days of dexamethasone treatment (40 μg/animal per day) did not alter the frequency of spontaneous GH pulses in conscious, freely-moving animals. The amplitude of the GH pulses in saline and dexamethasone-treated rats was different ( P < 0.01), the latter group having a higher incidence of GH levels less than 95 ng/ml, a lower incidence of GH levels between 96 and 251 ng/ml, and a higher incidence of GH values greater than 480 ng/ml. A 20 μg/kg per day dose of dexamethasone was sufficient to significantly inhibit growth but was inadequate in enhancing the GH response to an acute injection of GHRH in anesthetized animals. These results support the concept that glucocorticoids exert their catabolic effects on somatic growth in peripheral tissues and not at the pituitary level.

The ontogeny of growth hormone in the human fetal pituitary

To examine the ontogeny of growth hormone synthesis and secretion in human fetus, growth hormone messenger ribonucleic acid was measured in 11 pituitaries from fetuses of 16 to 27 weeks of gestation by hybridization of cytosol ribonucleic acid with complementary deoxyribonucleic acid labeled with phosphate 32. Pituitary growth hormone content and serum growth hormone, thyroxine, and cortisol concentrations were assessed by radioimmunoassay. Growth hormone messenger ribonucleic acid content in the fetal pituitary increased from the early midtrimester, reaching a level 15.3 times higher at 27 weeks of gestation than the value at 16 weeks. However, growth hormone content in the pituitary showed no evident change during 16 to 21 weeks of gestation and started to increase after 22 weeks. Serum concentration of growth hormone was variable but always greater than 50 ng/ml, and the maximal level was observed at 20 weeks of gestation (141 ng/ml). Although serum thyroxine concentration in the fetuses showed no correlation with pituitary growth hormone content or serum growth hormone concentration, serum concentration of cortisol was correlated positively with growth hormone content in the fetal pituitary. These results suggest that the maturation of the growth hormone synthesis and secretion system in the fetal pituitary occurs after 22 weeks of gestation and that cortisol may play some role in the ontogenesis of growth hormone.

Pituitary concentration of GH messenger ribonucleic acid in rats with anterolateral hypothalamic deafferentation.

To study neuronal mechanism through which the hypothalamus exerts its influence on growth hormone (GH) synthesis, anterolateral hypothalamic knife cuts (ALHD) were used. After ALHD, GH messenger RNA (mRNA) content in the pituitary was reduced to 47% of the control value. Neither the prolactin mRNA level nor the total DNA content showed any significant change. In such animals, the serum GH level was significantly higher (184%) and pituitary GH content was lower (43%) than the control values. These results suggest that neuronal factor(s) outside the mediobasal hypothalamus plays an important role in the regulation of GH synthesis.

Introduction

The present study was undertaken to examine 1) the effect of phosphate restriction on growth hormone (GH) secretory dynamics in freely moving, chronically cannulated rats and 2) the effect of hypophysectomy on the renal adaptive responses to phosphate deprivation. Phosphate restriction led to an increase in renal brush-border membrane Na+-dependent phosphate transport (2,511 +/- 283 vs. 1,006 +/- 122 pmol.mg protein-1.15 s-1, P less than 0.001) and in the plasma concentration of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] (127 +/- 10 vs. 63 +/- 4 pg/ml, P less than 0.001). In contrast, phosphate deprivation had no effect on either amplitude or frequency of spontaneous GH secretory bursts and did not alter pituitary GH concentration. Hypophysectomy led to a decrease in brush-border membrane Na+-dependent phosphate transport (669 +/- 78 vs. 1,006 +/- 122 pmol.mg protein-1. 15 s-1, P less than 0.003) and to a fall in plasma 1,25(OH)2D (42 +/- 9 vs. 63 +/- 4 pg/ml, P less than 0.02). Phosphate restriction of hypophysectomized rats elicited a twofold increase in Na+-dependent phosphate transport (1,312 +/- 106 vs. 669 +/- 78 pmol.mg protein-1.15 s-1, P less than 0.001) but no rise in plasma 1,25(OH)2D. We conclude that the renal adaptive responses to phosphate deprivation are not mediated by specific alterations in pulsatile GH secretion. Moreover, we demonstrate that the adaptive increase in brush-border membrane phosphate transport occurs after hypophysectomy, is not dependent on increased vitamin D hormone production, and is most likely subject to a different regulatory mechanism.

Pituitary involvement in renal adaptation to phosphate deprivation

The present study was undertaken to examine 1) the effect of phosphate restriction on growth hormone (GH) secretory dynamics in freely moving, chronically cannulated rats and 2) the effect of hypophysectomy on the renal adaptive responses to phosphate deprivation. Phosphate restriction led to an increase in renal brush-border membrane Na+-dependent phosphate transport (2,511 +/- 283 vs. 1,006 +/- 122 pmol.mg protein-1.15 s-1, P less than 0.001) and in the plasma concentration of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] (127 +/- 10 vs. 63 +/- 4 pg/ml, P less than 0.001). In contrast, phosphate deprivation had no effect on either amplitude or frequency of spontaneous GH secretory bursts and did not alter pituitary GH concentration. Hypophysectomy led to a decrease in brush-border membrane Na+-dependent phosphate transport (669 +/- 78 vs. 1,006 +/- 122 pmol.mg protein-1. 15 s-1, P less than 0.003) and to a fall in plasma 1,25(OH)2D (42 +/- 9 vs. 63 +/- 4 pg/ml, P less than 0.02). Phosphate restriction of hypophysectomized rats elicited a twofold increase in Na+-dependent phosphate transport (1,312 +/- 106 vs. 669 +/- 78 pmol.mg protein-1.15 s-1, P less than 0.001) but no rise in plasma 1,25(OH)2D. We conclude that the renal adaptive responses to phosphate deprivation are not mediated by specific alterations in pulsatile GH secretion. Moreover, we demonstrate that the adaptive increase in brush-border membrane phosphate transport occurs after hypophysectomy, is not dependent on increased vitamin D hormone production, and is most likely subject to a different regulatory mechanism.

Hormone secretory patterns, pituitary characteristics and selected blood metabolites in feedlot steers implanted with growth stimulants

Twelve Charolais-crossbred steers (256 kg) received one of three treatments: non-implanted controls (C), implanted initially and at 84 days with 36 mg zeranol (Ralgro, R) and implanted initially and at 84 days with 200 mg of progesterone and 20 mg of estradiol benzoate (Synovex-S,S). All steers were fed a corn-based diet (calculated metabolizable energy 2.89 Mcal/kg dry matter) ad libitum. In a parallel comparative slaughter trial, rates of empty body protein accretion were increased 14% in R and 24% in S steers (P<.01). R and S steers in the present study had heavier pituitary weights (P<.001), more pituitary growth hormone content (P<.04) and more pituitary weight/unit live weight (P<.05) than did C steers. Cattle implanted with R or S exhibited an increased growth hormone (GH) secretory response to a pituitary challenge with thyrotropin releasing hormone (TRH). Plasma insulin profiles were not significantly altered, but tended to be greater for steers given implants. Overall 9-hr GH secretory profiles were not affected by implantation. Plasma urea N at 94 days post-implantation was decreased (P<.01) by implantation. Plasma glucose was increased (P<.04) at both 94 and 199 days in R and S vs C steers. Overall mean and total (integrated area) plasma GH, as well as secretory profile components (baseline mean, amplitude of secretory spikes) were negatively correlated with body weight and size on days 94 and 199. Overall mean, baseline and integrated area of plasma insulin on days 94 and 199 were positively related to body weight and size. Thus positive protein anabolic growth responses from implantation (parallel comparative slaughter trial) were coupled with increased pituitary GH content and little change in circulating plasma GH concentrations between implanted and control steers. This may suggest that changes in tissue sensitivity, an increased plasma clearance rate of GH and/or a direct effect on target tissues may be involved in the improved growth performance of cattle implanted with R or S.