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J W Simpkins

Publications and source records attributed to J W Simpkins.

At least 145 records · Page 8Linked to original sources
PubMed1983

Effects on male sex behavior and preoptic dopamine neurons of hyperprolactinemia induced by MtTW15 pituitary tumors.

We have earlier reported that dopamine (DA) activity in the preoptic anterior hypothalamic (POA-AH) region of castrated rats is inhibited by testosterone and accelerated by PRL. These results suggested that dopaminergic neurons may play an important role in male copulatory behavior, particularly in the attenuation of sex behavior reported to be associated with hyperprolactinemia. We have now examined the effects of severe hyperprolactinemia on the POA-AH DA activity in association with any modifications of copulatory behavior. Sexually experienced adult male rats were castrated and implanted sc with Silastic implants containing testosterone to maintain serum testosterone levels in the range found in intact rats. Hyperprolactinemia was induced by inoculation of minced MtTW15 PRL secreting pituitary tumor fragments. Copulatory behavior was assessed at weekly intervals in hyperprolactinemic and control rats. During the period of tumor growth serum PRL levels increased logarithmically. Whereas sexual activity continued to improve in control rats, there was a marked decrease in several important parameters of copulatory behavior in hyperprolactinemic rats. The most dramatic decrease occurred in the percentage of tumor-bearing rats ejaculating which decreased progressively to zero at 6 weeks after tumor inoculation. Ejaculation frequency decreased and ejaculation latency increased in tumor-bearing rats before the complete disappearance of ejaculatory behavior. The deficits in copulatory behavior of hyperprolactinemic rats were accompanied in parallel studies by significant depletions of DA concentrations in the POA-AH. Further, neuronal activity, as evidenced by the turnover rates measured by rate of loss of DA after tyrosine hydroxylase inhibition with alpha-methyl paratyrosine, was markedly augmented in the POA-AH of hyperprolactinemic rats as compared to control animals. These findings disclose a close association between the acceleration in POA-AH DA activity and the attenuation of copulatory behavior induced by hyperprolactinemia and suggest the probability of an underlying role of the POA-AH DA neurons in male sex behavior normally induced by testosterone.

Animals↗
PubMed1983

Cysteamine induces depletion of both immunological and biological prolactin activity in the anterior pituitary and blood of the rat.

Previous studies have shown that cysteamine [2-aminoethanethiol (CSH)], given in vivo or in vitro, rapidly but reversibly depletes immunoreactive PRL from the anterior pituitary (AP) through a mechanism which, in vitro, does not appear to involve the dopamine (DA) receptor. In the present investigation, these effects of CSH were explored further with emphasis on determining whether CSH; (1) depletes biological as well as immunological PRL activity from the AP and blood, (2) has effects on plasma PRL in chronically cannulated male rats, (3) alters the PRL response to drugs which stimulate the secretion of the hormone, and (4) acts in vivo via DA receptors to deplete PRL. CSH produced a dose-dependent depletion of both immunological and biological PRL activity from the AP and blood. In chronically cannulated animals, PRL levels in the plasma were undetectable 90 min after CSH administration and remained so for 4 h. However, by 24 h plasma PRL in treated animals had returned to control levels. The PRL response to both domperidone and morphine was virtually abolished in CSH-treated animals. Blockade of DA receptors by pretreatment with domperidone did not alter the ability of CSH to reduce AP PRL stores. These results indicate that CSH: 1) alters both biological and immunological PRL activity by a rapid but reversible effect, and 2) circumvents the DA receptor to deplete pituitary PRL content. Thus, CSH or similar compounds may serve as a prototype for a new class of drugs which can be used in the treatment of hyperprolactinemia.

Animals↗
PubMed1983

Naloxone blocks the effects of delta 9-tetrahydrocannabinol on serum luteinizing hormone and prolactin in rats.

The present study was undertaken to determine if the effects of delta 9-tetrahydrocannabinol on gonadotropin secretion are mediated through endogenous opioid neurons in the rat. Ovariectomized rats were treated with estradiol-benzoate (EB, day O) and with progesterone (P) at 11:00 h on day 2. At 13:00 h (day 2), these estradiol primed and progesterone-treated (EBP) animals received either delta 9-THC (3mg/kg in oil, i.m.); naloxone (Nal) 3 mg/kg in saline, s.c.) or delta 9-THC + Nal. All animals were decapitated at 16:00 h and trunk sera were assayed for luteinizing hormone (LH) and prolactin (Prl), while medial basal hypothalami (MBH) were assayed for luteinizing hormone-releasing hormone (LHRH). Naloxone enhanced the EBP-induced hypersecretion of LH by 2-fold while delta 9-THC completely blocked the EBP-induced secretion of LH. delta 9-THC slightly diminished the stimulatory effect of Nal on LH secretion and caused a 2-fold increase in serum Prl concentrations, while Nal did not influence the serum PRL levels in these EBP rats. However, Nal did block the stimulatory effects of delta 9-THC on Prl secretion. delta 9-THC caused a significant increase in MBH content of LHRH, an effect which was prevented by Nal. These results suggest that the inhibitory effects of delta 9-THC on serum LH and the stimulatory effect of the cannabinoid on Prl are mediated by an opioid mechanism.

Animals↗
PubMed1982

Chronic hyperprolactinemia depletes hypothalamic dopamine concentrations in male rats.

The tuberoinfundibular dopamine (TIDA) system appears to tonically inhibit pituitary prolactin secretion while moderate elevations in serum prolactin levels, in turn, augment the turnover rate of dopamine (DA) without affecting the steady state concentrations of DA in the TIDA neurons (1-5). The present study demonstrates that chronic elevations in serum prolactin, to greater than 2,000 ng/ml, induced by the prolactin secreting MtTW15 tumor, decreased DA concentrations by 47% in the median eminence-arcuate nucleus (ME-ARC) region, by 43% in the medial basal hypothalamus (MBH) and 14% in the preoptic area-anterior hypothalamic region (POA-AH) without influencing the norepinephrine levels in these regions. Thus, chronic stimulation of hypothalamic DA neurons by prolactin may lead to depletion of DA concentrations and this may be an important factor in the reduced DA levels observed in hyperprolactinemia of senescent rats or that produced by chronic estrogen treatment.

Adenoma↗
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↗
PubMed1981

Alterations in daily rhythms of testosterone and progesterone in old male rats.

Studies were undertaken to characterize the daily patterns of secretion of testosterone (T), progesterone (P) and dihydrotestosterone (DHT) in young (3-4 months old) and old (19-20 months old) male Sprague-Dawley rats. In young rats, plasma T concentrations show dramatic daily variations with peak and nadir levels at 1130 and 2330 h, respectively. In old male rats, no such rhythmic pattern in plasma T was observed. Plasma P concentrations varied significantly in both young and old male rats, with peak levels occurring 8 h (1930 h) after the plasma T peak in young rats. Additionally, in old male rats, the daily increase in plasma P was significantly larger and was sustained for a longer period than in young rats. Plasma DHT concentrations were similar and changed little during the day in both young and old animals. In view of the known P influence on gonadal secretion, the possible significance of these age-related changes in daily patterns in plasma P and T are discussed.

Aging↗
PubMed1981

Hyperprolactinemia counteracts the testosterone-induced inhibition of the preoptic area dopamine turnover.

The present study was undertake to determine the effects of hyperprolactinemia on dopamine (DA) concentrations and turnover rates in the medial basal hypothalamus (MBH) and the preoptic area-suprachiasmatic nucleus region (POA-SCN) in castrated and castrated, testosterone(T) implanted male rats. Subcutaneous implants, which raised serum T levels to those found in intact rats, decreased serum LH to basal levels but did not alter DA turnover in the MBH. Anterior pituitary (AP) transplants under the renal capsule increased serum prolactin to 60-110 ng/ml, and accelerated DA turnover by nearly 2-fold in the MBH of both castrated and castrated, T-implanted rats without influencing serum LH levels. While T implants caused a decrease in the POA-SCN DA turnover, high serum prolactin levels produced by AP implants in castrated rats were ineffective in altering POA-SCN DA turnover. However, in the presence of physiological levels of T, these elevated serum prolactin levels not only blocked the T-induced decrease in POA-SCN DA turnover, but further augmented DA turnover over that observed inthe castrated or castrated, T-implanted rats. These results indicate that (i) for acceleration of the MBHDA turnover by prolactin T priming is not essential and it appears to occur at serum prolactin levels which fdo not depress serum LH levels, and (ii) the stimulatory effects of prolactin on the POA-SCN DA turnover are dependent upon the presence of circulating T. Since these synergistic effects of prolactin and T on the POS-SCN DA turnover are not involved in the regulation of gonadotropin secretion, their participation in attenuation of male sexual behavior associated with hyperprolactinemia is discussed.

Animals↗
PubMed1981

Progesterone-induced changes in hypothalamic luteinizing hormone-releasing hormone and catecholamines: differential effects of pentobarbital.

The effects of pentobarbital (Pnt) treatment on the progesterone (P)-induced afternoon increase in the medial basal hypothalamic (MBH) LHRH and serum LH and FSH levels in ovariectomized estradiol benzoate-primed rats were studied. Pnt injection before P blocked the afternoon rise in serum gonadotropins but failed to alter the increase in the MBH LHRH levels. Moreover, when Pnt was injected 150 min after P, the MBH LHRH content continued to rise to levels 25-37% above those seen in control rats. Analyses of LHRH concentrations in discrete hypothalamic nuclei revealed that the Pnt-induced accumulation was confined mainly to the median eminence, with a small increase in the suprachiasmatic nuclei region. P administration increased the MBH norepinephrine activity and concurrently decreased dopamine activity. Pnt was ineffective in suppressing the MBH LHRH response in these rats, but drastically reduced norepinephrine and accelerated dopamine turnovers in the MBH. These studies show 1) no definitive cause and effect relationship of the increments in MBH LHRH either with LH release (or LHRH release) or with changes in hypothalamic catecholamines induced by P treatment, and 2) that the striking rise in the MBH LHRH levels in estradiol benzoate-primed rats may represent formation of new immunoreactive LHRH predominantly in the median eminence region.

Animals↗
PubMed1980

Effects of a prolactin-secreting pituitary tumor on hypothalamic, gonadotropic and testicular function in male rats.

The presence of a transplanted prolactin- and GH-secreting pituitary tumor (Furth MtT.215) in inbred male rats resulted in increased hypothalamic LHRH and pituitary LH content, decreased serum LH and testosterone concentrations, and very high serum prolactin values. The pituitary tumor also inhibited LH release by the in situ pituitary in response to orchidectomy, or orchidectomy, or adrenalectomy, and reduced the LH response to LHRH administration. Testes weight was significantly reduced and adrenal weight was significantly increased in the rats carrying pituitary tumors. These results that inhibitory effects of the transplanted pituitary tumor on LH and testosterone secretion were affected both a reduction in hypothalamic LHRH release and a reduced responsiveness of the pituitary to LHRH.

Adrenalectomy↗
PubMed1980

Inhibitory effects of androgens on preoptic area dopaminergic neurons in castrate rats.

The present study was undertaken to determine the effects of androgen implants in the preoptic area-suprachiasmatic nucleus (POA-SCN) on catecholamine turnover in the POA-SCN and the medial basal hypothalamus (MBH) in orchidectomized rats. Bilateral implants of testosterone (T) or dihydrotestosterone (DHT) in the POA-SCN of orchidectomized rats did not affect serum concentrations of LH and FSH or the turnover of dopamine (DA) and norepinephrine (NE) in the MBH. In the area surrounding the implants in the POA-SCN, T and DHT decreased dopamine turnover by 67 and 37%, respectively, without influencing the POA-SCN norepinephrine turnover. These results indicate (i) that T implants in the POA-SCN selectively depress POA-SCN dopamine turnover, (ii) that this effect of T may occur following its conversion to DHT, and (iii) that these androgen effects probably do not mediate the negative feedback action of T on gonadotropin secretion.

Androgens↗
PubMed1980

Effects of pentobarbital on hypothalamic catecholamines and LRH activities.

Pentobarbital (Pnt) injection at 12.30 h to ovariectomized rats suppressed the LRH contents of the medial basal hypothalamus (MBH) in association with a significant fall in serum LH 60-90 min later. The LRH contents in the preoptic area (POA) were unchanged in Pnt treated rats. A similar effect on LRH levels in the MBH was also evident in ovariectomized rats pre-treated with oestradiol benzoate. Pnt administration rapidly reduced the noradrenergic (NE) turnover in the MBH and POA, whereas dopamine (DA) turnover was unaltered. These studies show that: (i) the apparent decrease in LRH secretion (release + contents) following Pnt treatment was associated with a fall in the hypothalamic NE neurotransmission, and (ii) LRH neurons and fibres in the MBH alone respond to Pnt treatment.

Animals↗