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Biomedical subjects

L J Forman

Publications and source records attributed to L J Forman.

53 records · Page 3Linked to original sources

Immunoreactive beta-endorphin in the plasma, pituitary and hypothalamus of young female rats on the day of estrus and intact and chronically castrated old constant estrous female rats.

Immunoreactive beta-endorphin (IR-beta-ENDO) was compared in the plasma, pituitary and hypothalamus of young female rats on the day of estrus and old constant estrous (CE) female rats, and in intact and chronically castrated old CE female rats. The concentration of IR-beta-ENDO in the plasma and the content and concentration of IR-beta-ENDO in the neurointermediate lobe of the pituitary were significantly greater in the old CE female rats than in the young female rats on the day of estrus. The content and concentration of IR-beta-ENDO in the anterior pituitary and hypothalamus were similar in the two age groups. To determine if estrogen contributed to the increase in plasma and pituitary levels of IR-beta-ENDO observed in the old animals, a group of old CE female rats were castrated and compared to sham operated control CE rats. Thirty days after castration, levels of plasma, pituitary and hypothalamic IR-beta-ENDO were comparable in the intact and the chronically castrated old female rats. These data indicate that in old CE female rats, plasma and pituitary IR-beta-ENDO are significantly increased in comparison to young female rats on the day of estrus, and that these increased levels of IR-beta-ENDO observed in old female rats do not appear to be influenced by gonadal estrogen.

Aging↗

Elevation of plasma LH in response to systemic injection of beta-endorphin antiserum in adult male rats.

A single injection of beta-endorphin antiserum into mature male rats produced approximately a 3-fold rise in plasma LH levels by 10 to 50 min, and declined by 90 min, but remained significantly elevated above pre-injection values. Control rats injected with normal rabbit serum showed no elevation in plasma LH values. These results indicate that beta-endorphin is one of the endogenous opiates that tonically depresses basal release of LH in mature male rats.

Animals↗

L-dopa restores amplitude of growth hormone pulses in old male rats to that observed in young male rats.

35 male Sprague-Dawley rats, 18 months old, were injected subcutaneously with the catecholamine precursor, L-dihydroxyphenylalanine (L-dopa) (100 mg/kg, twice daily), or vehicle alone, for 8 days in an attempt to increase the amplitude of growth hormone (GH) pulses in old male rats. 40% of young rats had at least one GH pulse greater than 600 ng/ml, over a 6.5 h sampling period, whereas only 22% of old vehicle-treated rats had pulses of similar amplitude. Treatment of old rats with L-dopa increased the number of animals showing elevated GH pulses to 53%. Young animals had mean GH concentrations of 136.5 +/- 14.0 ng/ml over the 6.5 h sampling period, whereas vehicle-treated old animals had mean GH levels of 95.2 +/- 7.7 ng/ml (p less than 0.05). Treatment of old animals with L-dopa increased mean plasma GH concentrations to 132.9 +/- 11.2 ng/ml (p less than 0.05) which was not significantly different from GH values in young rats. Pituitary GH concentration was less in old than in young rats (301 +/- 27.4 vs. 370 +/- 17.4 micrograms/mg protein, p less than 0.05). L-Dopa increased pituitary GH concentrations in old rats to 318 +/- 32.2 micrograms/mg protein, which was not significantly different from that in either young or old vehicle-treated animals. Hypothalamic somatostatin content in both rostral and caudal areas was lower in old than in young rats (p less than 0.01), and L-dopa had no significant effect on somatostatin content. These data indicate that L-dopa can increase the amplitude of GH pulses and elevate mean plasma GH in old male rats to levels present in young male rats, probably by increasing hypothalamic catecholamines.

Age Factors↗

Immunoreactive beta-endorphin in the plasma, pituitary and hypothalamus of young and old male rats.

Immunoreactive beta-endorphin (IR-beta-ENDO) was measured in the plasma, pituitary, and hypothalamus of young (3-5 mo.) and old (19-23 mo.) male Sprague-Dawley rats, using a specific radioimmunoassay. Plasma IR-beta-ENDO in old male rats (3.44 +/- 0.54 ng/ml) was more than three times higher than values observed in young male rats (1.00 +/- 0.10 ng/ml). Pituitary content and concentration of IR-beta-ENDO also were significantly greater in the old (5.85 +/- 0.51 microgram/gland and 1.17 +/- 0.10 microgram/mg protein) than in the young (3.53 +/- 0.29 microgram/gland and 0.78 +/- 0.06 microgram/mg protein) male rats. The content of IR-beta-ENDO in the hypothalamus of old and young rats was nearly the same (43.45 +/- 2.47 and 49.88 +/- 6.35 ng/hypothalamus, respectively), whereas the concentration of IR-beta-ENDO in the hypothalamus of the old male rats (3.89 +/- 0.25 ng/mg protein) was approximately 50% lower than that observed in the young male rats (7,80 +/- 0.85 ng/mg protein). These changes in plasma, pituitary, and hypothalamic IR-beta-ENDO may contribute to the increase in prolactin and decrease in gonadotropins observed in old male rats, since beta-ENDO administration is known to produce these effects on prolactin and gonadotropin secretion.

Aging↗

Effects of CNS active drugs and somatostatin antiserum on growth hormone release in young and old male rats.

The capacity of several potent pharmacological agents to increase growth hormone (GH) release was tested in young (3- to 4-month-old) and old (18- to 20-month-old) male Sprague-Dawley rats. Young and old animals were injected with alpha-methyl-p-tyrosine (250 mg/kg), a catecholamine synthesis inhibitor, followed 60 min later by the alpha-adrenergic receptor agonist, clonidine hydrochloride (150 micrograms/kg). Plasma GH levels increased to greater than 276 ng/ml by 30 and 50 min in young rats, whereas values never exceeded 130 ng/ml (p less than 0.01) in old rats. Piribedil methane sulfonate (1 mg/kg), a dopamine receptor agonist, significantly increased GH in young animals 60 min after injection (p less than 0.01), but had no effect in old rats. Morphine sulfate (5mg/kg) increased plasma GH concentration in young rats to greater than 400 ng/ml at 30, 50 and 70 min after injections, whereas values in old animals never exceeded 300 ng/ml (p less than 0.01). 15 min after injection of somatostatin antiserum No. 774 (5 ml/kg), plasma GH levels increased to greater than 750 ng/ml in both young and old rats. Administration of greater volumes of somatostatin antiserum (8 ml/kg) increased GH levels more in old than in young animals 30 and 45 min after injection (p less than 0.01). These results indicate that old male rats have less capacity to increase GH in response to agents that normally enhance GH release. This may be the result of a diminished number of affinity of post-synaptic neurotransmitter receptors, or to an increased release of somatostatin. Since somatostatin antiserum in creased H equally or to a greater extent on old that in young animals, aging rats may release more somatostatin or the pituitary may be more sensitive to the inhibitory effects of this hormone.

Aging↗

Maintenance by L-DOPA treatment of estrous cycles and LH response to estrogen in aging female rats.

Nineteen, non-cycling female rats, 13-15 months of age, were fed 125 mg L-DOPA/15 g feed daily, and nineteen control rats of the same age were provided feed without L-DOPA. Sixteen of the L-DOPA fed rats each demonstrated 1-7 (average = 3) vaginal estrous cycles during the 75-day period of treatment, whereas no cycles were observed in the untreated controls. All animals were then ovariectomized and the post-castration rise in LH was monitored. Four weeks after ovariectomy, serum LH levels in the L-DOPA treated old female rats were significantly higher than in the non-treated old female rats. A single injection of 20 micrograms of estradiol benzoate (EB) significantly lowered serum LH in the L-DOPA treated rats, but no effect was observed in the non-treated controls. A second injection of EB three days later produced a significantly greater LH surge in the old rats given L-DOPA than in the non-L-DOPA treated controls. These results indicate that prolonged L-DOPA administration can partially prevent the decline in function of the hypothalamo-pituitary-ovarian system in aging female rats.

Aging↗

Decreased pulsatile release of growth hormone in old male rats.

Pulsatile release of GH was compared in young (4-5 months old) and old (18-20 months old) male Sprague-Dawley rats using indwelling atrial cannulae. More than 57% of the young rats exhibited GH pulses greater than 300 ng/ml plasma, whereas only 7% of the old animals had GH pulses of similar amplitude. Trough GH values were not different between young and old rats, but during the 10.5-h sampling period, mean GH concentrations in young male rats were significantly greater than those in old male rats (175.3 +/- 20.9 vs. 70.2 +/- 7.6 ng/ml; P < 0.01). In another experiment, pituitary GH and hypothalamic somatostatin content were measured in young and old rats. The pituitary GH content was significantly greater in young than in old males (1187 +/- 95 vs. 670 +/- 93 microgram; P < 0.01). The immunoreactive somatostatin content in caudal areas of the hypothalamus was also greater in young than in old male rats (100.2 +/- 4.2 vs. 79.0 +/- 5.1 ng; P < 0.01). These observations demonstrate that GH secretion is depressed in old male rats, and this is associated with diminished pulsatile release of GH. The results also suggest that a relationship exists among the reduction in somatostatin content, pituitary GH content, and attenuated GH secretion in old male rats.

Aging↗

A potential vaccine for cocaine abuse prophylaxis.

Presently, there are estimated to be 1.5 to 2.0 million individuals infected with HIV-1 in the U.S. and about 12 million worldwide. In the U.S. over 90% of reported cases of AIDS occurred among two subgroups, homosexual males and intravenous substance abusers (IVSAs). Currently, there is no anti-cocaine addiction medication available. In order to explore vaccination as an alternative means for protection against cocaine addition, we immunized inbred male Fisher rats with either cocaine emulsification in complete Freund adjuvant (CFA) or with cocaine conjugated with keyhole limpet hemocyanin (KLH), as carrier plus CFA. Animals were initially immunized with 0.1 mg/animal of cocaine or cocaine-KLH. Animals were given a booster with the corresponding agents after 4 weeks. Ten animals/group were used. Controls received normal saline at the time of immunizations. These animals were injected, intraperitoneally, with 25 mg/kg of cocaine, and were examined for the analgesic effect of cocaine by the hot plate method. The average analgesic effect of cocaine was significantly reduced (p greater than 0.03) in animals immunized with cocaine-KLH (13.77 s) as compared to saline controls (21.6 s). Fifty percent of the animals (5/10) in the cocaine-KLH group and 33% of the animals (3/9) in the cocaine immunized group appeared completely resistant to the effect of cocaine on the central nervous system (CNS). We also have determined the levels of cocaine-specific antibodies produced by each animal by an ELISA method. Degree of protection from cocaine seems to correlate well with the amount of anti-cocaine antibodies produced by each animal (-0.61).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mediation by gonadal steroids of plasma beta-endorphin and LH in castrated female and male rats.

Immunoreactive beta-endorphin (IR-BE) was significantly decreased and luteinizing hormone (LH) significantly increased in female rats castrated for four weeks. Forty eight hours after a single injection of estradiol benzoate (EB), IR-BE levels increased, and LH levels were reduced. On the afternoon following the administration of a second injection of EB given six hours earlier, IR-BE levels were reduced below control values, whereas LH levels were significantly elevated. There was no change in IR-BE levels during the remainder of that afternoon whereas LH levels decreased over time. Similar to female rats, IR-BE was diminished and LH increased in castrated male rats. IR-BE was increased significantly above those values observed in intact animals 24 hr after a single injection of TP and returned to control levels by 48 hr after administration of TP. Injection of TP reduced LH to levels observed prior to castration. These findings suggest that gonadal steroids exert a feedback on the release of IR-BE from the pituitary of female and male rats opposite to their feedback effect on the release of pituitary gonadotropins.

Animals↗

Neurotransmitters and estrogen interact to affect beta-endorphin levels in castrated female rats.

The possibility of an interaction between neurotransmitter systems and estrogen in affecting levels of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP), the neurointermediate lobe of the pituitary (NIL) and the hypothalamus was investigated in ovariectomized (OVX) female rats. Chronic administration of the dopamine antagonist, haloperidol (HALO), had no effect on IR-BE levels in the AP. By contrast, the content of IR-BE in the NIL was increased and the content of IR-BE in the hypothalamus was decreased by HALO. Chronic treatment with estradiol benzoate (EB) produced a decrease in IR-BE in all three tissues. The effect of EB on IR-BE levels in the AP and NIL was reversed by administration of HALO, while EB and HALO appeared to act independently on the hypothalamus. Gel chromatography indicated that alterations in IR-BE in the AP corresponded to similar changes in beta-endorphin (BE) and beta-lipotropin (LPH) and that BE alone comprised the immunoreactivity detected in the NIL and hypothalamus regardless of treatment. Chronic treatment with the alpha-adrenergic agonist, clonidine (CLON), increased, whereas treatment with EB decreased, IR-BE levels in the AP, NIL and hypothalamus. EB attenuated the effect of CLON on IR-BE levels in the AP and hypothalamus. Chronic treatment with CLON appeared to promote the formation of BE in the AP, whereas the proportions of BE and LPH were similar in the AP of controls and animals treated with EB or EB and CLON. BE alone was detected in the NIL and hypothalamus of treated and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characterization of beta-endorphin- and alpha-MSH-related peptides in rat heart.

POMC-derived peptides and mRNA have been identified in heart tissue, although POMC processing has not been fully characterized. In the present study, we found that beta-lipotropin and ACTH were localized in rat heart, although they were almost entirely converted to beta-endorphin- and alpha-MSH-related peptides. Ion exchange HPLC analysis revealed that beta-endorphin(1-31) was further processed to alpha-N-acetyl-beta-endorphin(1-31), which comprised 35.9 +/- 0.1% of total immunoreactivity, and smaller amounts of beta-endorphin(1-27), beta-endorphin(1-26), and their alpha-N-acetylated derivates. The predominant alpha-MSH immunoreactive peptides coeluted with alpha-MSH and N,O-diacetyl-alpha-MSH by reverse-phase HPLC, although small amounts of ACTH(1-13)-NH2 were also present. Thus, multiple forms of beta-endorphin and alpha-MSH are localized in rat heart. beta-Endorphin(1-31) is a minor constituent, however, indicating that nonopioid beta-endorphin peptides predominate.

Adrenocorticotropic Hormone↗

The elevation of immunoreactive beta-endorphin in old male rats is related to alterations in dopamine and serotonin.

The concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP) and the neurointermediate lobe of the pituitary (NIL) was elevated in old as compared to young male rats. Treatment of old male rats with the dopamine precursor, L-DOPA, did not affect the concentration of IR-BE in the AP and produced a significant reduction in the concentration of IR-BE in the NIL. By contrast, administration of the serotonergic neurotoxin, p-CPA, significantly diminished the concentration of IR-BE in the AP of old male rats, while the concentration of IR-BE in the NIL remained unchanged. Hypothalamic IR-BE was decreased in old male rats and was not influenced by administration of L-DOPA or p-CPA. Chromatographic analysis indicated that in the AP of old animals the amount of beta-endorphin relative to beta-lipotropin was increased and was diminished slightly by the treatments. Alterations in IR-BE in the NIL and hypothalamus were represented solely by beta-endorphin. These data suggest that in old male rats, a decrease in dopaminergic activity contributes to the increase in IR-BE levels in the NIL, and an increase in serotonergic function, at least in part, is responsible for the elevation in the level of IR-BE in the AP.

Animals↗