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Biomedical subjects

J W Simpkins

Publications and source records attributed to J W Simpkins.

At least 163 records · Page 9Linked to original sources
PubMed1979

Blockade of progesterone-induced increase in hypothalamic luteinizing hormone-releasing hormone levels and serum gonadotropins by intrahypothalamic implantation of 6-hydroxydopamine.

The present study was undertaken to identify the hypothalamic locus where norepinephrine (NE) nerve terminals communicate with luteinizing hormone-releasing hormone (LH-RH)-containing neurons involved in the stimulatory feedback action of gonadal steroids on LH and FSH release. Ovariectomized rats received estradiol benzoate (10 microgram/rat s.c.) on day 0. Intracranial implants containing either 6-hydroxydopamine (6-OHDA), to destroy NE terminals, or cocoa butter (controls) were placed bilaterally in the suprachiasmatic nucleus (SCN), medial basal hypothalamus (MBH) or olfactory tubercle (OT) on day 1. Progesterone (P, 5 mg/rat s.c.) was administered at 10.00 h on day 2 to elicit increases in serum LH and FSH and the MBH LH-RH levels in the afternoon. Implantation of 6-OHDA in the SCN resulted in a marked depletion of NE in and around the region of the SCN in the preoptic-anterior hypothalamic area (POA-AH) without adversely affecting dopamine (DA) concentrations, and blocked the P-induced afternoon increase in the MBH LH-RH and serum gonadotropin levels. Similar reduction in the MBH NE concentrations occurred following placement of 6-OHDA in the MBH; however, these as well as implants in the OT were ineffective in suppressing the P-induced effects. These studies show that functional integrity of the SCN regions is critical in manifestation of the P-induced rise in the MBH LH-RH activity, and this region in the POA-AH, therefore, may be the primary locus of synaptic communication between NE terminals and LH-RH neurons.

Animals↗
PubMed1979

Blockade of steroid-induced leuteinizing hormone release by selective depletion of anterior hypothalamic norepinephrine activity.

Female Sprague-Dawley rats, weighing 200--225 g, were ovariectomized and, 10 days later, were given a single sc injection of 10 micrograms estradiol benzoate/100 g BW. Three days after estradiol benzoate treatment, animals received 50 micrograms progesterone (P)/100 g BW, resulting in a surge in LH release 7 and 9 h later. To determine the locus of the noradrenergic component of the P-induced LH surge, 6-hydroxydopamine (6-OH-DA), a neutrotoxin, was implanted into either the suprachiasmatic region or the median eminence (ME) 24 h before P administration. An implant of 6-OH-DA in the suprachiasmatic region decreased anterior hypothalamic norepinephrine concentration by 83%, anterior hypothalamic dopamine concentration by 24%, and eliminated the P-induced LH surge. ME implant of 6-OH-DA decreased norepinephrine concentration by 57% without affecting dopamine concentration, but was unable to alter the P. induced LH surge. These results indicate that the anterior hypothalamic noradrenergic system is necessary for the P-induced LH surge in ovariectomized rats and that noradrenergic nerve terminals in the ME are not involved in this process.

Animals↗
PubMed1978

Relation of biogenic amines to onset of puberty in the female rat.

Changes in hypothalamic concentration and turnover index (TI) of norepinephrine (NE), dopamine (DA), and serotonin (5HT) were studied during the first estrous cycle at the onset of puberty. Rats were killed when 40% of the population showed open vaginas. They were classified according to the state of their reproductive tract and serum LH values, as in anestrus, early proestrus, late proestrus, estrus, or diestrus. Serum LH, PRL, and hypothalamic LHRH were measured by RIA. The TIs for DA and NE were measured by estimating their rate of decrease after administration of alpha-methyl-para-tyrosine, and for 5HT-TI by its increase after pargyline administration. An increase in NE-TI in the hypothalamus was observed between anestrus and early proestrus, a decrease in DA-TI during early and late proestrus, and a small increase in 5HT-TI between early and late proestrus. LH and PRL peaks were observed at late proestrus when DA-TI and NE-TI reached their lowest values and hypothalamic LHRH concentration was failing. After late proestrus, the DA-TI rose sharply, NE-TI remained essentially unchanged. 5HT-TI fell, and serum LH and PRL declined to basal levels. These results suggest that the LH and PRL surges at late proestrus during the first estrous cycle at puberty are associated with an increase in NE-TI at early proestrus, a progressive decline in DA-TI at early and late proestrus, and an increase in 5HT-TI at late proestrus.

Animals↗
PubMed1977

Evidence for depressed catecholamine and enhanced serotonin metabolism in aging male rats: posssible relation to gondotropin secretion.

The steady state concentration of dopamine (DA), norepinephrine (NE), and serotonin (5HT) was determined and turnover estimated in several brain regions of young (3-4 months) and old (21 months) male Wistar rats. An estimate of DA and NE turnover was obtained by determining their depletion rates after treatment with alpha-methylpara-tyrosine, a tyrosine hydroxylase inhibitor. Serotonin turnover was estimated by determining its rate of increase after monoamine oxidase inhibition with pargyline. In old males, medial basal hypothalamic (MBH) DA concentration and depletion rate were significantly lower than in young males. DA concentration of the remaining hypothalamus also was lower in old than in young males, but depletion rates were not different. DA concentration and depletion rate in the olfactory tubercle were the same in both age groups. The steady state concentration of NE in the MBH and remaining hypothalamus, and the hypothalamic NE depletion rate, were significantly lower in old than in young animals. In both brain and hypothalamus, steady state concentrations of 5HT were the same in young and old rats, but by 30 min after monoamine oxidase inhibition with pargyline, hypothalamic, but not brain, 5HT increased more in old than in young males. This may indicate a greater turnover of 5HT in the hypothalamus of old than of young males. In non-drug treated (control) old male rats, serum LH and FSH were lower, serum prolactin was higher and serum TSH was the same in young male rats. These data suggest that a decrease in catecholamine and an increase in serotonin metabolism occur in the hypothalamus of old male rats. These changes may be related to the decrease in release of gonadotropins and increase in release of prolactin observed in these old male rats.

Aging↗
PubMed1976

Serum and pituitary TSH and response to TRH in developing male and female rats.

Serum and pituitary thyroid-stimulating hormone (TSH) was measured by radioimmunoassay in male and female Sprague-Dawley rats from 21 through 80 days of age. In males, serum TSH levels increased progressively from days 30 through 50, and were found to be lower on days 60, 70, and 80. In females, serum TSH levels were elevated on days 40 and 50, compared with day 30, but declined on days 60-80. A sex difference in serum TSH levels, with those of the male higher than those of the female, appeared by day 30 and was maintained through day 80. The anterior pituitary (AP) content of TSH in males increased from days 21 through 50 and remained constant through day 80; in females the AP content increased between days 25 and 60 and remained constant through day 80. In males, thyrotropin-releasing hormone (TRH) induced a significant elevation in serum TSH at all ages tested, but was less effective in increasing serum TSH on day 25 than on days 15 or 40 or in 3-4-month-old rats. The response to TRH appeared to be sustained longer in adults than in all other age groups. These observations indicate that serum TSH levels increase in both male and female rats at about the time of puberty and then decline, and that changes in the response to TRH may account in part for the increase in serum TSH levels during development.

Age Factors↗
PubMed1976

The temporal interaction of corticosterone and prolactin in affecting liver lipid metabolism of the chick.

Experiments were conducted to determine if Brown Leghorn chickens (Gallus domesticus) showed a daily differential responsiveness to the phased injections of corticosterone and prolactin. In experiment 1, 28 day old chicks, maintained on continuous lighting and a standard diet, were treated daily for 6 days with corticosterone (300 mug. in 0.2 cc. saline) and with prolactin (150 mug. in 0.2 cc. saline) for 4 days. The prolactin injections began 2 days after the first corticosterone injection. The interval between daily corticosterone injections at 1800 hours followed by prolactin injections 6, 12 or 18 hours later resulted in a significant increase in the liver lipidcontent in the chicks. However, when corticosterone and prolactin were given at the same time (1800 hours), no increase in liver lipid content was observed. Corticosterone admininstered at 6oo hours and followed by prolactin injections had no effect on liver lipid content regardless of the time of prolactin prolactin injections. Experiment 2 was designed to test the effect of the administration of corticosterone or prolactin alone at either 600 hours or 1800 hours on liver lipid metabolism. Two groups of Brown Leghorn chicks received prolactin alone (for 2 days) at either 600 hours or 1800 hours. None of these treatment groups were significantly different from the uninjected controls. It is concluded that the chick has a diurnal sensitivity to the effects of coritcosterone and that once the liver is affected by corticosterone, a temporal interaction between this steroid and prolactin can affect the liver lipid content of the Brown Leghorn chick.

Animals↗
PubMedDate not supplied

Growth hormone and thyrotropin secretory profiles and provocative testing in aged rats.

The impact of aging on both basal and induced GH and TSH secretion in male and female rats was investigated. Analysis of the individual GH secretory profiles in young (3-4 month) and old (19-20 month) rats indicated that sex-dependent patterns of GH secretion was preserved in old animals. However, we observed a reduction of individual GH peak amplitudes of 66% in old males and 53% in old females when compared to their respective young animals. Further, the GH response to an intravenous bolus of GH-releasing factor (GRF), morphine and clonidine was dramatically blunted or absent in old male and female animals. In contrast to GH, basal TSH secretion was elevated, while the TSH response to thyrotropin-releasing hormone (TRH) was not significantly affected in old animals of either sex. The present data provide evidence that reduced pituitary sensitivity to GRF may be a possible cause for reduced GH secretion in old animals. Further, the elevation in plasma TSH observed in old animals is not the result of an increased pituitary sensitivity to TRH.

Aging↗
PubMedDate not supplied

Effects of aging on morphine withdrawal in the rat.

Little is known about the effects of aging on the process of opiate dependence and withdrawal in the rat. The present study was undertaken to quantitate naloxone-precipitated opiate withdrawal in young (3-4 months old) and aged (24 month old) Long-Evan female rats. Following addiction to morphine, young and aged rats were evaluated for tail skin temperature (TST), rectal temperature (Tr), behavior, rhinorrhea, lacrimation, salivation, and diarrhea in response to naloxone administration. Young rats showed the expected TST increase and Tr decline in response to withdrawal. By contrast, aged rats showed two distinct TST response subgroups. The majority of aged rats showed an exaggerated TST response to naloxone, while some aged rats failed to exhibit any TST response to withdrawal. This latter subgroup showed significantly lower basal Tr than either the young rats or the aged-responders. The behavioral activating effects of opiate withdrawal were blunted in aged rats, and these old animals showed a marked decline in rhinorrhea, lacrimation, and salivation during withdrawal. The diarrheal response during withdrawal was not substantially different between the two groups. Collectively, these data indicate that aged female rats exhibit markedly different responses to opiate withdrawal than do their young counterparts.

Aging↗
PubMedDate not supplied

Age- and dose-dependent effects of neonatal monosodium glutamate (MSG) administration to female rats.

The age- and dose-dependent effects of neonatal MSG were evaluated in pre- and postpubertal female rats. The neurotoxic action of MSG was assessed by examining monoamine content in microdissected regions of the mediobasal hypothalamus. MSG was administered at a dose of 4 mg/g on postnatal days 2 and 4 (MSG-Lo) or on postnatal days 2, 4, 6 and 8 (MSG-Hi). MSG-Hi treatment significantly reduced dopamine (DA) content in the arcuate nucleus (ANH) and lateral median eminence (LME) on postnatal day 21 when compared to NaCl-injected controls. DA content relative to controls was not altered in the ANH or LME postnatal or postnatal day 60 in MSG-Hi, however, norepinephrine (NE) was significantly (p less than 0.05) decreased on both postnatal day 21 and 60 in the LME. MSG-Lo treatment significantly (p less than 0.05) reduced ANH NE content on postnatal day 60 compared to controls. Both MSG-Hi and MSG-Lo treatment increased 5-hydroxyindoleacetic acid content in the preoptic area (POA) on postnatal day 60 relative to the controls. Developmental changes independent of MSG treatment were noted in the hypothalamus. DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content in the POA were 2-3-fold higher on postnatal day 21 compared to postnatal day 60. In contrast, DA content increased with age in the ANH, LME and medial ME. NE content in the ANH increased as a function of age in controls, but not in MSG-treated rats. The effects of MSG treatment on the postnatal development and maturation of neurons in the mediobasal hypothalamus were discussed in relation to the direct neurotoxicity of MSG.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Polycyclic phenols, estrogens and neuroprotection: a proposed mitochondrial mechanism.

Polycyclic phenols, including the estrogens, have been shown to be potent neuroprotectants in a variety of cellular and animal model systems. Although classical estrogen receptor interactions and consequent responses play a role in certain circumstances, the neuroprotective activity of polycyclic phenols that do not interact with estrogen receptors ERalpha or ERbeta is more likely to be through non-genomic mechanism(s). We propose here that such non-feminizing polycyclic phenols exert their protective effects at least in part by stabilizing mitochondria, preventing apoptotic and/or necrotic forms of cell death that are associated with mitochondrial dysfunction. Consistent with this mitochondrial model and the available data, these compounds protect neurons and other cell types from a wide variety of pathologically relevant stressors.

Adenosine Triphosphate↗