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K S Estes

Publications and source records attributed to K S Estes.

32 records · Page 2Linked to original sources
PubMed1984

Age-related alterations in dopamine and norepinephrine activity within microdissected brain regions of ovariectomized Long Evans rats.

The ability of several stimuli which augment central catecholamine (CA) neuronal activity to reinitiate estrous cycles in old constant estrous (CE) rats suggests CA neuronal function is impaired with advanced age. We examined the effects of age on dopamine (DA) and norepinephrine (NE) levels and turnover rates within microdissected brain regions of previously normally cycling young (3-4 months old) and middle-aged (10 months old) and CE old (20-22 months old) Long Evans 2 weeks after ovariectomy. Steady-state DA concentrations were significantly decreased in old compared to young rats in the nucleus accumbens (34%), anterior hypothalamic nucleus (54%, NHA ), neurointermediate pituitary lobe (51%, NIL) and median eminence (74%, ME). The rate constant of DA loss, an estimate of neuronal activity, decreased in old versus young rats only in the preoptic area suprachiasmatica (60%, POAs ) and NHA (60%) and was unchanged or augmented in the 7 other regions. In contrast, a decline in DA turnover rate of 29-67% was observed in 6 of 9 regions in middle-aged rats and 45-81% in 5 of 9 regions in old rats. Steady-state NE concentrations similarly were significantly decreased in old versus young rats in the POAs (54%), medial forebrain bundle (44%), nucleus suprachiasmatica (49%) and ME (59%). The rate constant of NE loss progressively decreased with increasing age only in the POAs and was unchanged or augmented in other regions. Turnover rate of NE was decreased from 21 to 98% in 4 of 8 regions from old animals. A strong positive correlation was noted between the rate constant of NE (but not DA) loss measured in young rats and the magnitude of the age-related depletion in NE concentrations within specific brain regions. Collectively these data indicate that with increasing age: CA neuronal function is differentially altered in nuclei located along the preoptico-tuberal pathway; substantial declines in both DA and NE concentrations are the primary contributor to the reduced amine turnover noted in several of these regions; and the observed age-related alterations in CA turnover may contribute to impaired LH response and the persistent hyperprolactinemia in old CE rats.

Aging↗
PubMed1984

Age-related alteration in catecholamine activity within microdissected brain regions of ovariectomized Fischer 344 rats.

The effects of increasing age on catecholamine (CA) metabolism in microdissected brain regions and on serum and pituitary hormone levels were examined in ovariectomized Fischer 344 rats. Young (4 to 5 months old) and middle-aged (9 to 10 months old) normally cycling and old repeated pseudopregnant rats (21-22 months old, PP) were ovariectomized to eliminate the complicating effects of cyclic gonadal steroid fluctuations. CA metabolism was examined 2 weeks later. To determine CA turnover rates, each age-group was subdivided into three groups, which were killed by decapitation 0, 45, or 90 min after administration of alpha-methyl-para-tyrosine (alpha-mpt). Dopamine (DA) and norepinephrine (NE) concentrations were determined in microdissected brain regions by radioenzymatic assay, and turnover rates were estimated. Steady-state concentrations of NE were not altered in middle-aged rats, but NE turnover rates increased in middle-aged rats in five of the six areas examined. While NE concentrations did not change with age in the median eminence (ME), NE turnover rates increased significantly in the two older age groups. These data indicate that the age-related decline in NE concentrations in several ventral diencephalic nuclei is preceded by a period of hyperactivity in noradrenergic neurons. DA concentrations were generally decreased in most areas examined in old versus young rats, with dramatic DA depletions (42-78%) observed in five regions. However, no consistent relationship between DA concentrations and turnover rates was seen either in regions with stable DA levels or in those which showed an age-associated decrease in DA concentrations. In the ME, a 42% decline in DA concentration was associated with an increase in the DA turnover rate in the oldest group of rats. Serum luteinizing hormone (LH) levels were similar in all three age groups of ovariectomized rats, while serum prolactin was elevated four-fold in old compared to younger animals. These data indicate that a complex pattern of regional alterations in CA metabolism accompanies the aging process and these may be related to the pseudopregnant state and hormone secretory capacity of aging Fischer 344 rats.

Age Factors↗
PubMed1983

Cysteamine depletes prolactin in young and old hyperprolactinemic rats.

Studies were undertaken to evaluate the effects of cysteamine on serum and anterior pituitary concentrations of prolactin in hyperprolactinemic female rats. Serum prolactin was elevated in young (4 to 5 months old) rats by implantation of 17 beta-estradiol while 26- to 28-month-old rats were in constant estrus and exhibited an age-related hyperprolactinemia. At 4 h after treatment with cysteamine (90 mg/kg body wt) serum and anterior pituitary prolactin concentrations were reduced in young animals by 98 and 85%, respectively. In old constant-estrous rats, cysteamine reduced serum prolactin by 92% and anterior pituitary prolactin by 82%. In young pseudopregnant rats, cysteamine induced a prompt resumption of estrous cycles. These studies indicate that cysteamine is an effective depletor of serum and pituitary prolactin in hyperprolactinemic rats.

Aging↗
PubMed1982

Normal LHRH neuronal function and hyperprolactinemia in old pseudopregnant Fischer 344 rats.

The relative contributions of LHRH neuronal function and hyperprolactinemia to the maintenance of the repeated pseudopregnant (PP) state in old Fischer 344 rats were examined. LHRH concentrations within 8 microdissected regions of the preoptico-tuberal pathway were not different between normally cycling 4-5 and 10-11 months old rats and PP 22-23 months old rats. LHRH concentrations were significantly decreased in the median eminence and serum LH was increased 2 weeks after ovariectomy in all 3 age groups. Ovariectomy had no significant effect on LHRH concentrations in any of the other brain regions examined in these three age-groups. Serum prolactin levels were elevated 4-fold in old PP rats when compared to younger animals and these old PP rats failed to exhibit the normally observed decline in serum prolactin in response to ovariectomy. Daily treatment for 10 days with the dopamine agonist, CB-154, reinitiated normal ovarian cycles in 7 of 7 old PP rats while vehicle treatment was ineffective in altering the PP state. The data suggest that persistent hyperprolactinemia rather than impaired LH secretory mechanisms is primarily responsible for the PP state in old Fischer 344 rats.

Age Factors↗
PubMed1982

Altered hypothalamic dopamine depletion rate and LHRH content in noncyclic hamsters.

Effect of light deprivation on hypothalamic dopamine (DA) depletion rate and luteinizing hormone releasing hormone (LHRH) content was evaluated in golden hamsters. Hamsters maintained in continuous darkness (CD) became acyclic after about 6 weeks while another group of hamsters maintained vaginal cyclicity under 20 lux light intensity for 14 hours a day. All hamsters were ovariectomized subsequently. Luteinizing hormone releasing hormone levels were significantly higher in the medial basal hypothalamus (MBH) and the serum gonadotropin levels were significantly lower in CD hamsters when compared with 20 lux group. However, gonadotropin release in response to exogenous LHRH was not significantly different in CD or 20 lux group of hamsters. Examination of hypothalamic catecholamine levels one hour after alpha-methyl-p-tyrosine injection indicated that the DA depletion was higher in CD animals. Results indicate that light deprivation probably enhances DA depletion rate in the MBH, suggesting that increased activity in dopaminergic neurons may inhibit the release of MBH LHRH in hamsters kept in continuous darkness.

Animals↗
PubMed1982

Resumption with clonidine of pulsatile LH release following acute norepinephrine depletion in ovariectomized rats.

The effects of adrenergic stimulation on the pulsatile release of LH were investigated in ovariectomized rats with acute depletion of brain norepinephrine (NE) levels. Rats bearing atrial cannula were pretreated with NE synthesis inhibitors, diethyldithiocarbamate (DDC) or bis (4-methyl-1-homopiperanzinyl thiocarbanyl) disulfide (FLA-63) and blood was withdrawn at 15-min intervals beginning 1 h later. DDC and FLA-63 markedly dampened pulsatile LH secretion. Administration of the alpha-adrenergic agonist clonidine (CLON) resulted in immediate LH release and apparent resumption of pulsatile LH secretion. The facilitatory effect of CLON on LH secretion was was more pronounced in FLA-63 than in DDC-pretreated rats. Additional characterization of the pattern of LH secretion in FLA-63-pretreated rats showed that the interval between LH pulses was significantly lengthened after acute NE depletion; however, CLON treatment increased LH pulse frequency to that found in ovariectomized rats. To further investigate the ability of CLON to augment pulsatile LH release, the LH secretory pattern was determined between 2 and 4 h after CLON administration FLA-63-pretreated rats. 8 of 10 rats receiving CLON (0.3 mg/kg) responded with episodic LH release 2-4 h following treatment while saline-treated rats continued to show dampened LH secretory patterns. These studies demonstrate that following acute depletion of NE in ovariectomized rats, a single injection of CLON can enhance both the amplitude and frequency of LH pulses. Further, the data suggest that central noradrenergic neurons exert only a permissive effect on pulsatile LH release and that the pulsatile mechanism may predominately be resident in LHRH neurons.

Animals↗
PubMed1979

Isolation and partial characterization of prolactin from equine pituitary gland (hypophysis).

Highly purified equine prolactin was prepared from equine pituitary glands (hypophysis) by serial extractions with water at pH 5.5, 0.1 M (NH4)2SO4 at pH 4.0, and 0.25 M (NH4)2SO4 at pH 5.5 to remove other hormones, and then finally with 70% ethanol at pH 9.3 to 10.0 to extract prolactin. Preliminary purification of the extract involved salting out other substances with 0.1% NaCl at pH 9.0. Prolactin was precipitated out by adding three times the volume of 95% ethanol at 4 C. This prolactin preparation had a biological potency of 24 IU/mg. Further purification by isoelectric focusing on a pH gradient of 5 to 7 gave three prolactin components with the following characteristics: isoelectric point 5.8, 5.7, and 5.25; biological potencies (IU/mg) 35.6, 19.6, and 11.3. The major component had a molecular weight of 25,000, an isoelectric point of 5.8, and a biological potency of 35.6 IU/mg. Antiserum produced against this component did not cross-react with equine follicular stimulating hormone, luteinizing hormone, and growth hormone, but did cross-react with ovine and bovine prolactin. Human and murine prolactin had little cross-reactivity with the equine prolactin antiserum.

Animals↗
PubMedDate not supplied

Development of a non-surfactant formulation for alfaxalone through the use of chemically-modified cyclodextrins.

The poor water solubility of alfaxalone (less than 5 micrograms/mL), a useful steroid anesthetic agent, was dramatically increased via complexation with a series of four cyclodextrins. The most effective agent was 2-hydroxypropyl-beta-cyclodextrin (2HPCD) which solubilized alfaxalone in a linear manner as a function of concentration. At a 2HPCD concentration of 50% w/v, approximately 80 mg/mL of alfaxalone was dissolved indicating an increase in aqueous solubility of over four orders of magnitude. The cyclodextrin solution was stable to autoclaving and could be conveniently lyophilized to yield a solid product.

Anesthetics↗