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Biomedical subjects

S M Gabriel

Publications and source records attributed to S M Gabriel.

At least 37 records · Page 2Linked to original sources
PubMed1993

Influence of in vivo reproductive endocrine state on growth hormone-releasing factor stimulated adenylate cyclase activity in anterior pituitary fragments.

The growth hormone releasing factor (GRF) stimulated adenylate cyclase activity was evaluated in membrane fractions of anterior pituitary glands from male and female rats and in gonadectomized rats following in vivo gonadal steroid treatments. The baseline adenylate cyclase activity was lower in random estrous cycle female rats as compared with males. When estrous cycle phases were evaluated, diestrus 1 females had a lower basal activity as compared with males, while proestrus females were similar to males. The maximal stimulation of adenylate cyclase activity by GRF (i.e. Vmax) was lower in random estrous cycle female rats than in males. This lower Vmax, relative to males, was more pronounced in diestrus 1 than in proestrus females. There was little difference in the ED50 for GRF-stimulated adenylate cyclase activity among these groups. The adenylate cyclase activity was altered 1 week after gonadectomy or 1 week after gonadectomy plus simultaneous in vivo gonadal steroid treatment. The expression of data as a function of whole tissue (content) or as a function of protein (concentration) influenced magnitude and direction of these treatment effects. This may reflect the proliferation of nonsomatotroph cell populations and altered protein synthetic activity following reproductive endocrine manipulations. When expressed as a whole tissue content, the baseline adenylate cyclase activity was unchanged after gonadectomy when compared to same-sex, gonadal-intact cohorts. However, an increase in the Vmax for GRF-stimulated adenylate cyclase activity was found in gonadectomized rats relative to sham-operated, gonadal-intact cohorts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1992

Growth hormone pulsatility and the endocrine milieu during sexual maturation in male and female rats.

Although a sexually dimorphic pattern of rat growth hormone (rGH) secretion is well recognized in adult rats, episodic rGH release has been incompletely characterized in younger rats. In the present study, 28 to 113-day-old rats received jugular catheters and were housed in chambers designed for stress-free blood sampling. Three to seven days after surgery, 300 microliters of blood was withdrawn every 10 min between 16.00 and 22.00 h. Pulsatile rGH secretion before 33 days of age was similar in males and females. Low baseline rGH secretion was interspersed with infrequent, low amplitude pulses. In early puberty, between 33 and 40 days of age, rGH pulse amplitudes increased more than tenfold in both sexes. The duration of rGH pulses was significantly greater at this time in males versus females, a pattern that continued though adulthood. By late puberty, between 41 and 54 days of age, rGH pulse amplitudes similarly increased twofold in both sexes. Baseline rGH secretion increased at this time in both sexes, with females having a higher baseline compared to males. Only in adult rats over 54 days of age, was the typical pattern of low basal rGH secretion, combined with high amplitude, low frequency rGH pulses in males versus females evident. A sex difference in body weight, i.e. males weighing more than females, became evident after day 33 of age. This sex difference was preceded by an increase in testosterone in males versus females at all ages examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

The growth hormone response to clonidine in acute and remitted depressed male patients.

The growth hormone (GH) response to clonidine was evaluated in 28 acutely depressed male patients, 17 remitted depressed patients, and 26 normal control subjects. The GH response to clonidine was blunted (delta less than 4 ng/ml) in a significantly increased proportion of both acute and remitted patients compared to control subjects. Covarying for age effects, the GH response to clonidine (as area-under-the-curve) was not significantly different between any of the three groups, but was significantly diminished in both the acute and remitted depressed patients who were ever hospitalized for an episode of depression, compared to control subjects. Six patients studied in both the acute and remitted states were blunted in both states. These findings could not be accounted for by other clinical and demographic variables including weight, time off antidepressants, severity of current depressive symptoms, and subtype of depression. These results raise the possibility that the blunted GH response to clonidine may represent a state-independent correlate of some forms of severe depression. Issues regarding the specificity and interpretation of this finding require further clarification.

Acute Disease↗
PubMed1990

Galanin-like immunoreactivity is influenced by estrogen in peripubertal and adult rats.

Galanin gene expression in the anterior pituitary is potently stimulated by estrogen in adult rats. To evaluate the influence of estrogen on galanin during the peripubertal period 30- to 32-day-old female rats were treated with pregnant mare serum gonadotropin (PMSG, 10 IU s.c., 10.00 h). Galanin-like immunoreactivity (galanin-LI) in hypothalamic and pituitary tissues was evaluated 1, 2 or 3 days after PMSG treatment between 17.00 and 19.00 h. The PMSG treatment stimulated 17 beta-estradiol secretion, which induced a midafternoon LH surge 2 days after the PMSG treatment. Concentrations of galanin-LI at the time of this LH surge were elevated 82% in the anterior pituitary and 58% in the hypothalamus (without the median eminence) when compared to saline-treated female rats. On the 3rd day after the PMSG injection, galanin-LI was increased 236% in the anterior pituitary, 88% in the neurointermediate lobe and 39% in the median eminence compared to saline-treated female rats. These changes in galanin-LI were not observed in similarly aged male rats or ovariectomized rats treated with PMSG. In adult male rats, daily injections with 17 beta-estradiol valerate (10 micrograms/daily s.c.) for 1 week increased galanin-LI in the median eminence and neurointermediate lobe to an extent similar to that seen in juvenile female rats following PMSG treatment. In contrast, the high serum levels of 17 beta-estradiol achieved after 17 beta-estradiol valerate treatment increased galanin-LI in the anterior pituitary 65-fold. These studies indicate that galanin-LI is influenced by estrogen in peripubertal and adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Sexual differentiation of growth hormone feedback effects on hypothalamic growth hormone-releasing hormone and somatostatin.

To investigate possible sex differences in the feedback regulation of growth hormone (GH) secretion, concentrations of immunoreactive GH-releasing hormone (GRF) and somatostatin (SS) were measured in the median eminence (ME) and the hypothalamus of male and female rats bearing the MtTW15 tumor, which secretes high amounts of GH and prolactin (PRL). Four weeks after tumor implantation in male rats, the GRF concentration in the whole hypothalamus, including the ME, was decreased by 37% (0.29 +/- 0.02 vs. 0.46 +/- 0.02 ng/mg protein in intact male controls; p less than 0.001) and the concentration of SS was increased by 40% (11.5 +/- 0.7 vs. 8.1 +/- 0.3 ng/mg protein in male controls; p less than 0.01). In female rats, the presence of tumor for 4 weeks caused a smaller (18%) reduction in GRF concentrations (0.27 +/- 0.02 vs. 0.33 +/- 0.03 ng/mg protein in intact female controls; p less than 0.05) and no significant change in SS concentrations (10.2 +/- 0.08 vs. 9.7 +/- 0.8 ng/mg protein in female controls). Tumor-related changes in GRF and SS concentrations were also more pronounced in male rats than in females, when determined separately in the microdissected ME and in the remaining hypothalamus. These differences occurred despite similar increases in serum GH, PRL and insulin-like growth factor I concentrations in male and female tumor-bearing rats. To assess which hormone (GH or PRL) was responsible for these changes, intact male rats were treated for 10 days with 2 daily s.c. injections of rat GH (rGH; 100 and 250 micrograms/day), rat PRL (100 and 250 micrograms/day) or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Influence of thyroid hormone on the concentration of galanin in the rat brain and pituitary.

Galanin (GAL) is a 29-amino acid peptide implicated in neuroendocrine regulation of prolactin, growth hormone and thyrotropin in the rat. GAL-like immunoreactivity and GAL messenger RNA (mRNA) are present in the anterior pituitary (AP) and hypothalamus and the expression of GAL mRNA has been shown to be modulated by peripheral gonadal steroid hormones. In view of possible interactions between members of the steroid/thyroid hormone receptor family and recent data suggesting an effect of GAL on thyrotropin secretion, we investigated the possible influence of thyroid status on GAL concentrations in the hypothalamus and AP of the male rat. Three weeks after the surgical removal of the thyroid gland from male rats, the concentrations of GAL in the median eminence (ME) and AP were reduced 54 and 65%, respectively. Similarly, GAL concentrations were decreased 39% in the ME and 69% in the AP of animals rendered hypothyroid by treatment with propylthiouracil (PTU). The effects of PTU treatment in both regions were reversed by daily T4 injections (50 micrograms/kg). The effects of PTU in the ME were reversed after 2 weeks of T4 treatment, whereas 3 weeks of replacement therapy were required to restore GAL concentrations in the AP. However, T4 treatment of intact control animals did not influence GAL concentrations. This study demonstrates that the presence of thyroid hormones is required for the maintenance of physiological concentrations of GAL in the hypothalamus and AP of the rat. These data also suggest that GAL may be involved in the negative feedback regulation of the hypothalamohypophysial-thyroid axis.

Animals↗
PubMed1990

Opiate-thyroid hormone interactions in the regulation of thyrotropin secretion in the rat.

Studies were performed to determine the role of thyroid hormone in the suppression of thyrotropin (TSH) by opiates. Serum samples were collected by decapitation 1, 3, 6, 12, 24, or 48 h after rats were implanted with 1 sustained-release morphine (75 mg) or placebo pellet. Morphine decreased TSH by 44% at 1 h and by 83% at 3 h, and TSH remained significantly depressed by 38% through 48 h. Thyroxine (T4) levels were significantly reduced from 12 to 24 h after morphine, but triiodothyronine (T3) levels were not affected. When control or thyroidectomized (THX) rats were implanted with morphine or placebo 24 h before serum collection, morphine significantly decreased TSH, T3 and T4 in controls but had no effect on TSH in THX rats. Thus, it appears that the morphine-induced suppression of TSH release requires circulating thyroid hormone. When THX rats were chronically treated with morphine or placebo, then injected subcutaneously with saline or 1, 10 or 100 micrograms T4/kg body weight 24 h prior to serum collection, morphine treatment alone did not affect TSH in THX rats. T4 replacement caused a dose-dependent decrease in serum TSH in both morphine and placebo rats; however, TSH was suppressed significantly more in morphine than in placebo rats. Thus, while chronic morphine treatment is ineffective in suppressing in TSH in THX rats, morphine interacts with thyroid hormone to reduce TSH release. These data suggest that morphine may exert its inhibitory effect on TSH secretion by increasing the negative feedback sensitivity to thyroid hormones.

Animals↗
PubMed1989

Sex differences in vasoactive intestinal peptide (VIP) concentrations in the anterior pituitary and hypothalamus of rats.

Recent evidence suggests that vasoactive intestinal peptide (VIP), a putative prolactin (PRL)-releasing factor, is both synthesized and released by anterior pituitary cells, to act as a paracrine or autocrine factor. We have investigated the hypothesis that hypothalamic or pituitary VIP levels differ in male and female rats, since neuroendocrine control of PRL is sexually differentiated. Opposite sex differences were found in the hypothalamus and anterior pituitary. Random-cycle female rats had one-third higher VIP levels in the hypothalamus than males. In contrast, anterior pituitary VIP levels were 3 times as high in male rats as in females. Median eminence VIP levels were similarly low in both sexes. These results support a possible role of VIP in the sexually dimorphic regulatory mechanisms of PRL secretion. Moreover, demonstration that hypothalamic and pituitary VIP levels vary in opposite directions suggests that VIP is differentially regulated at the two sites.

Animals↗
PubMed1989

A pharmacological analysis of food intake regulation in rats treated neonatally with monosodium L-glutamate (MSG).

Studies were conducted to examine deficits in food intake regulation in MSG-treated rats that result from known or suspected damage to neurotransmitter systems involved in feeding. Male rats were injected with either MSG (4 mg/g) or sodium chloride on postnatal days 2 and 4 (MSG-Lo) or postnatal days 2, 4, 6 and 8 (MSG-Hi). As adults, MSG-treated and control rats (n = 12/group) were examined for deficits in pharmacologically elicited feeding and other measures of food intake regulation. A second group of MSG-treated (n = 9/group) and control rats (n = 12) were used to measure basal blood pressure and nociceptive reactivity in adulthood. Organ weights, body weight and neuropeptide Y (NPY) content in brain regions were determined at the end of the study. MSG-Hi rats consumed significantly less food than controls during the dark part of the light cycle. Both MSG-Hi and MSG-Lo groups ate significantly less food than controls after a 48-hour fast. MSG-Hi and MSG-Lo rats consumed significantly less food than controls in response to 1.0 mg/kg morphine. MSG-Hi rats consumed significantly less food than controls during the dark phase and significantly more food than controls during the light phase in response to naloxone (1.0 mg/kg). MSG-Lo ate significantly more than controls in response to 0.1 mg/kg guanfacine. MSG-Hi and MSG-Lo showed a significant attenuation in diazepam-stimulated feeding when compared to controls. Blood pressure was significantly lower in both MSG-Hi and MSG-Lo rats compared to controls. Tail flick latencies were not altered by MSG-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Potential involvement of galanin in the regulation of fluid homeostasis in the rat.

A physiological role for galanin, a 29-amino acid neuropeptide, has not been established. However, anatomical studies have demonstrated the presence of galanin in brain regions associated with the control of water balance in the rat, most notably in the paraventricular nucleus (PVN) of the hypothalamus and the neurointermediate lobe of the pituitary gland (NIL). In the PVN, galanin coexists with arginine vasopressin (AVP) in magnocellular neurons. The present study demonstrates that homozygous Brattleboro rats, which lack AVP, produce galanin. Galanin concentrations in the median eminence (ME) of the homozygous Brattleboro rat do not differ from the galanin concentrations in the ME of either heterozygous Brattleboro or Sprague-Dawley rats. However, galanin concentrations in the NIL of the homozygous Brattleboro rat were reduced by 75%. Similarly, dehydration induced by salt-loading reduced galanin concentrations in the NIL and produced transient changes in the ME. These data demonstrate that galanin concentrations are influenced by changes in fluid homeostasis and suggest that galanin may be an important component in the regulation of neurohypophyseal function and AVP secretion.

Animals↗
PubMed1989

Iso stimulation of GH and cAMP: comparison of beta-adrenergic- to GRF-stimulated GH release and cAMP accumulation in monolayer cultures of anterior pituitary cells in vitro.

Growth hormone (GH) release and cAMP content were measured in monolayer cultures of anterior pituitary cells after beta-adrenergic and GH-releasing factor (GRF) receptor activation. Isoproterenol (Iso, ED50-20 nM) was less potent than GRF (ED50-20 pM) in stimulating GH release. Iso caused a rapid stimulation of GH release that was maximal after 15 min and declined thereafter, while GRF caused a more gradual increase in GH secretion that was maximal after 30 min and remained elevated after 3 h. Both Iso- and GRF-stimulated GH release were preceded by an increase in cAMP content in the pituitary cells. Further, the addition of 3-isobutyl-1-methylxanthine (IBMX) to the medium enhanced the GH-stimulatory and cAMP-accumulating effects of both secretagogues. Experiments performed with native catecholamines and synthetic catecholamine agonists and antagonists indicated that the GH-stimulatory effect of Iso was mediated by a mixed population of beta 1-adrenergic and beta 2-adrenergic receptors. Additionally, experiments performed with cultured GH3 tumor cells, found that incubation with GRF, Iso, vasoactive intestinal polypeptide, forskolin, or cholera toxin caused an increase in cAMP content in the cells. However, compared to the responses observed in primary pituitary cultures the GH secretory response to these agents was comparatively small. Together, these studies suggest that a mixed population of beta 1-adrenergic and beta 2-adrenergic receptors may act, at least in part, on somatotrophs in the anterior pituitary to stimulate GH release. Although both GRF and beta 2-adrenergic receptor agents affect GH release through a common second messenger system, their differing pharmacokinetic properties suggest distinct intracellular mechanisms.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Sexual and developmental differences in peptides regulating growth hormone secretion in the rat.

Sex differences in the hypothalamic control of growth hormone (GH) secretion were investigated by measuring rat GH-releasing factor (rGRF) and somatostatin in male and female rats. Rat GRF-like immunoreactivity (rGRF-IR) was higher in the median eminence and hypothalamic tissue outside of the median eminence of adult (90-day-old) male compared to female rats. A similar pattern of rGRF-IR content was found in the median eminence of 35-day-old rats. This sex difference developed between days 25 and 35 of age, during which time serum concentrations of insulin-like growth factor (IGF-1) and body weight increased in both sexes. To a lesser extent, the content of somatostatin-like immunoreactivity (SLI) was higher in the median eminence of adult female rats compared to male rats. Whole hypothalamic rGRF-IR and SLI contents were influenced only moderately by adult gonadectomy or gonadal steroid treatments. For example, estrogen increased rGRF-IR content in castrated rats, but orchidectomy alone or orchidectomy followed by testosterone did not influence rGRF-IR content. Additionally, whole hypothalamic SLI content was unaffected by orchidectomy or orchidectomy followed by testosterone or estrogen. One month after ovariectomy, rGRF-IR and SLI in whole hypothalamic fragments were similar to their respective contents in gonad-intact males. However, ovariectomy followed by estrogen or testosterone did not restore rGRF-IR content and partially restored SLI content to levels seen in gonad-intact females.

Aging↗
PubMed1988

Chronic morphine and testosterone treatment: effects on norepinephrine and serotonin metabolism and gonadotropin secretion in male rats.

The effects of sustained-release implants of morphine (M) and/or testosterone (T) on serum gonadotropin levels and norepinephrine (NE) and serotonin (5-HT) metabolism in brain regions were examined. While 4 days of M or 5 mm [corrected] T treatment were without significant effect, the combination dramatically decreased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Castration increased NE content of the mediobasal hypothalamus (MBH), and although M, 5 mm [corrected] T, or their combination significantly reduced NE levels in the MBH, they remained elevated compared to intact or 30 mm [corrected] T-treated rats. Further, in the MBH no differences in normetanephrine (NME) levels, nor in NME:NE ratios, nor 5-HT metabolism were evident. In the preoptic area-anterior hypothalamus, NE or 5-HT metabolism were not altered by castration and M and/or T. These results show that M and T interact to suppress LH and FSH release in the apparent absence of any appreciable effect on hypothalamic monoamines.

Animals↗
PubMed1988

Characterization of galanin-like immunoreactivity in the rat brain: effects of neonatal glutamate treatment.

Concentrations of the neuropeptide, galanin, were measured using a newly characterized radioimmunoassay in brain regions of adult male rats treated neonatally with monosodium glutamate. Galanin-like immunoreactivity (galanin-IR) was significantly reduced 57% in the median eminence, 15% in the medial basal hypothalamus, and 27% in the septal region when compared to untreated littermates. Concentrations of galanin-IR were reduced 22% in the preoptic region and unchanged in the parietal cortex. These studies suggest that glutamate-sensitive, galanin-containing neurons in the arcuate nucleus project to regions of the basal forebrain of the rat in addition to the median eminence. The galanin projection from the arcuate nucleus to the median eminence suggests that this peptide plays a role in the regulation of anterior pituitary hormone secretion.

Age Factors↗
PubMed1988

Galanin stimulates rat pituitary growth hormone secretion in vitro.

The effect of galanin on growth hormone (GH) secretion was investigated in monolayer cultures of rat anterior pituitary cells. Galanin caused a gradual increase in GH concentrations into the culture medium that was maximal at 90 minutes and sustained after 180 minutes. The ED50 for galanin-stimulated GH secretion was approximately 200 nM compared to an ED50 for rat GH-releasing factor (rGRF)-stimulated GH secretion of 10pM. Galanin and rGRF were additive in increasing GH release into the incubation medium. These data indicate that porcine-derived galanin has a direct effect on pituitary GH secretion in vitro.

Animals↗
PubMed1988

Galanin is an estrogen-inducible, secretory product of the rat anterior pituitary.

Galanin is a peptide widely distributed throughout vertebrate central and peripheral nervous systems. Although its precise physiologic role is unknown, it can stimulate the pituitary secretion of prolactin and growth hormone. We examined the control of rat galanin (rGal) gene expression in the anterior pituitary using RNA blot and in situ hybridization analyses and using specific RIA. Pituitaries of normal male and ovariectomized female rats contained little detectable rGal mRNA. Treatment of these animals with 17 beta-estradiol increased pituitary rGal mRNA up to 4000-fold. These increases depended on time and dose of estrogen administration and correlated with up to 50-fold increases in pituitary galanin-like immunoreactivity. Galanin-like immunoreactivity was detectable in the plasma of estrogen-treated animals. Pituitary levels of rGal mRNA in female rats varied greater than 30-fold during the estrous cycle, with a peak on estrus and a nadir on diestrus. Estrogen-induced rGal gene expression was also observed in transplantable MtTW15 prolactin- and growth hormone-containing tumors but not in neuronal tissues expressing this gene. These data demonstrate that rGal is a secreted product of rat anterior pituitary cells, where its gene expression is strongly affected by physiologic levels of circulating estrogen.

Animals↗