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G D Riegle

Publications and source records attributed to G D Riegle.

At least 19 recordsLinked to original sources

Responsiveness of tuberoinfundibular dopamine neurons in the aged female rat to the stimulatory actions of prolactin.

The autoregulatory feedback control of prolactin, which is mediated by tuberoinfundibular dopamine (DA) neurons, is altered in the aged rat; this is evidenced by increased circulating concentrations of prolactin and decreased activity of these neurons. In the present study the action of prolactin on tuberoinfundibular DA neurons in young and aged female rats was estimated by measuring the rate of DA synthesis (dopa accumulation following the administration of a decarboxylase inhibitor) in the median eminence. The rate of dopa accumulation in the median eminence of the aged (26 months) rat was reduced to 50-60% of that in the young (3 months) rat. The acute systemic administration of haloperidol, a DA antagonist which increases serum concentrations of prolactin or intracerebroventricular infusions of prolactin increased the rate of dopa accumulation in the median eminence of both young and aged rats by the same relative amount. The administration of haloperidol and prolactin increased the rate of DA synthesis to a greater extent in young than in aged rats. The administration of bromocriptine, a DA agonist which reduces serum concentrations of prolactin, decreased the rate of dopa accumulation in the median eminence of both young and aged rats. In young animals the intracerebroventricular administration of prolactin reversed the bromocriptine-induced decrease in DA synthesis in the median eminence after 4 h and caused a further increase after 12 h. Qualitatively similar effects were seen in the aged rats; however, prolactin-treated young rats had much higher levels of DA synthesis than aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Restraint stress decreases the neurosecretory activity of tuberoinfundibular dopaminergic neurons in young but not in aged female rats.

The regulation of prolactin secretion by tuberoinfundibular dopamine (DA) neurons appears to be altered in the aged rat: the concentration of prolactin in the serum increases and the activity of the tuberoinfundibular DA neurons decreases. In the young female rat a brief period of stress reduces the tuberoinfundibular DA neurosecretory activity and increases the secretion of prolactin. The purpose of the present study was to determine if the responsiveness of tuberoinfundibular DA neurons to restraint stress is altered in the aged female rat. The activity of these neurons was estimated from the rate of DA synthesis in their terminals in the median eminence, as measured by the rate of accumulation of dihydroxyphenylalanine (DOPA) after the administration of a decarboxylase inhibitor. Thirty minutes of restraint stress increased serum prolactin concentrations in both young (3 months) and aged (26 months) constant estrous rats, but reduced the rate of DOPA accumulation in the median eminence of only the young rats. Restraint also decreased the rate of DOPA accumulation in the median eminence of intermediate-aged rats (14 months) independently of whether the rats were exhibiting normal ovarian cycles (measured on the day of estrus) or were in a constant estrus. This suggests that the loss of ovarian cyclicity per se is not associated with the age-related change in the response of tuberoinfundibular DA neurons to restraint stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The rapid 'tonic' and the delayed 'induction' components of the prolactin-induced activation of tuberoinfundibular dopaminergic neurons following the systemic administration of prolactin.

The present study was designed to characterize the time and dose relationships of the response of tuberoinfundibular dopaminergic (TIDA) neurons in the rat to systemically administered prolactin (PRL). The activity of TIDA neurons was estimated by measuring the rate of dopamine (DA) synthesis in the median eminence (DOPA accumulation following the administration of a decarboxylase inhibitor). Rats were pretreated with bromocriptine, a dopaminergic agonist, so as to inhibit the release of endogenous PRL from the anterior pituitary, and thereby reduce the activity of TIDA neurons to a 'basal' level from which it could be increased subsequently by exogenously administered PRL. In control animals an intraperitoneal injection of ovine PRL (oPRL) increased DOPA accumulation at 16 h, but not before, whereas in bromocriptine-pretreated animals an intraperitoneal injection of oPRL increased DOPA accumulation after 4 h ('tonic' component) and caused a further increase after 16 h ('induction' component). Continuous intravenous infusions of oPRL into bromocriptine-pretreated rats increased DOPA accumulation in the median eminence by 4 h, and when infused into control rats oPRL reduced serum concentrations of endogenous rat PRL (rPRL) by 2 and 4 h. Continuous intravenous infusions of rPRL increased DOPA accumulation in the median eminence after 2 h; this effect exhibited a very steep dose-response relationship (possibly an 'all-or-none' response). TIDA neurons were very sensitive to changes in circulating concentrations of PRL; their activity was increased if serum PRL concentrations were merely doubled by infusing a low concentration of rPRL for 4 h. Three daily injections of haloperidol elevated circulating rPRL concentrations and increased the rate of DOPA accumulation in the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Progesterone and luteinizing hormone secretion following stress-induced interruption of constant estrus in aged rats.

Concentrations of progesterone and luteinizing hormone (LH) were measured during the first diestrus and subsequent proestrus after constant estrous was interrupted by restraint stress. Stress stimulated an acute increase in serum progesterone. Although stress resulted in changes in vaginal cytology characteristic of normal estrous cycles, stress-treated constant estrous (CE) rats had no midcycle (diestrous day 1) elevation of progesterone and markedly lower LH and progesterone during the afternoon of proestrous than age-matched normally cycling controls. The majority of the treated rats resumed CE without completing a cycle. In a separate experiment, progesterone injection during proestrous resulted in increased LH secretion in aging rats with normal estrous cycles. These data indicate that decreased proestrous progesterone secretion may contribute to the decrease in neuro-endocrine stimulation of proestrous gonadotropin secretion in the aged rat and may be associated with the initiation of CE.

Aging↗

Hypoprolactinemia induced by hypophysectomy and long-term bromocriptine treatment decreases tuberoinfundibular dopaminergic neuronal activity and the responsiveness of these neurons to prolactin.

The effect of long-term decreases in circulating concentrations of prolactin was determined on the responsiveness of tuberoinfundibular dopamine (DA) neurons to this hormone. The activity of these neurons in ovariectomized rats was estimated by measuring the rate of DA synthesis (DOPA accumulation after the administration of a decarboxylase inhibitor) in the median eminence at various times after serum concentrations of prolactin had been reduced by hypophysectomy or the chronic administration of a DA agonist (bromocriptine, 3 mg/kg/day). The concentration of DA in the median eminence, but not in striatum, declined progressively up to 12 days after hypophysectomy, but did not change at any time during bromocriptine treatment. On the other hand, norepinephrine concentrations in the median eminence were increased 12 days after both treatments. Within 24 h after hypophysectomy or the first injection of bromocriptine the rate of DA synthesis in the median eminence was decreased; this decrease was maintained for at least 12 days suggesting that tuberoinfundibular DA neuronal activity is normally maintained by endogenous prolactin. Intracerebroventricular (ICV) injections of prolactin (10 micrograms, 12 h prior to sacrifice) increased the rate of DA synthesis in the median eminence of control, 24-hour hypophysectomized and 24-hour bromocriptine-treated rats. After longer periods (6-12 days) of bromocriptine treatment or after hypophysectomy the responsiveness of tuberoinfundibular DA neurons to prolactin was reduced. Dose-response studies revealed that the sensitivity and magnitude of response to ICV prolactin was markedly reduced in 12-day hypophysectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute restraint stress decreases dopamine synthesis and turnover in the median eminence: a model for the study of the inhibitory neuronal influences on tuberoinfundibular dopaminergic neurons.

The effects of acute stress on serum prolactin concentrations and tuberoinfundibular dopaminergic (TIDA) neuronal activity were studied in female rats. TIDA neuronal activity was estimated by measuring the rate of dihydroxyphenylalanine (DOPA) accumulation after the administration of a decarboxylase inhibitor (NSD 1015) and the rate of decline of dopamine (DA) after the administration of a tyrosine hydroxylase inhibitor (alpha-methyltyrosine) in the median eminence. Serum prolactin concentrations were increased following 30 min of supine immobilization (restraint stress), but returned to control levels by 2, 8, and 16 h after the onset of this stress. The rate of DOPA accumulation was decreased during the 30 min of restraint; it was still further reduced 2 h later but had returned to control levels 8 and 16 h later. No change in the rate of DOPA accumulation was observed in the striatum or neurointermediate lobe of the pituitary at any time after the start of restraint. Restraint stress also decreased the rate of DA turnover in the median eminence, but was without effect on the rates of DA turnover in the striatum or neurointermediate lobe. These results suggest that restraint stress activates an inhibitory neuronal pathway which decreases the activity of TIDA neurons and may be responsible, at least in part, for the increase in serum prolactin concentrations. The responsiveness of TIDA neurons to the stress-induced decrease in activity was not influenced by the time of day or the stage of the estrous cycle. Not all stressful manipulations decreased TIDA neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Acute restraint stress decreases tuberoinfundibular dopaminergic neuronal activity: evidence for a differential response in male versus female rats.

The basal activity o f tuberoinfundibular dopaminergic (TIDA) neurons is higher and the response of these neurons to the stimulatory actions of prolactin is greater in the female than in the male rat. In the female rat, the restraint-stress-induced increase in serum prolactin concentrations is accompanied by a concurrent decrease in the activity of TIDA neurons. The purpose of the present study was to compare these effects of restraint in male and female rats. TIDA neuronal activity was estimated by measuring the rate of dopamine (DA) synthesis (DOPA accumulation after the administration of a decarboxylase inhibitor, NSD 1015) and the rate of DA turnover (decline of DA after administration of a tyrosine hydroxylase inhibitor; alpha-methyltyrosine) in the median eminence. Thirty minutes of restraint increased serum prolactin concentrations in both male and female rats, but a greater response was observed in the females. Restraint also decreased the rates of synthesis and turnover of DA in the median eminence of the female but not the male rat. The difference in the response of TIDA neurons in male and female rats to restraint is not the consequence of neuronal differentiation resulting from neonatal androgen exposure, because restraint aso decreased the activity of TIDA neurons in androgen-sterilized female rats. The inability of restraint stress to reduce TIDA neuronal activity in the male rat appears to be the consequence of testosterone, since TIDA neurons were responsive to restraint following castration of the males.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Adenohypophysial dopamine content and prolactin secretion in the aged male and female rat.

In male rats the concentrations of dopamine (DA) in the adenohypophysis and of PRL in serum increase progressively with age. The increase in the DA content is not a consequence of reduced metabolism of DA, since the activities of the enzymes that deaminate (monoamine oxidase) and O-methylate (catechol-O-methyltransferase) this amine are not reduced in the anterior pituitary of aged male rats; indeed, both type A and B monoamine oxidase activities are increased in the pituitaries of aged rats. The increased DA present in the aged adenohypophysis is not in a static pool but, as in young rats, is rapidly decreased by pharmacological treatments that reduce the activity of tuberoinfundibular DA neurons (gamma-butyrolactone), reduce the synthesis of DA in these neurons (alpha-methyltyrosine), or block DA receptors (haloperidol) in the adenohypophysis. All of these treatments increased serum PRL levels and reduced DA concentrations in the adenohypophysis of both young and aged rats. Similarly, in female rats, where age-related differences in BW and body composition are minimized, serum PRL concentrations and DA concentrations in the adenohypophysis of both young and aged rats changed in the same way after the administration of a DA agonist (apomorphine) or a DA antagonist (haloperidol). Apomorphine reversed the alpha-methyltyrosine-induced increase in serum PRL concentrations and the decrease in anterior pituitary DA content in both young and aged rats, although the latter animals appear to be more responsive to this drug. Similarly, aged rats were more sensitive to the increase in serum PRL concentrations and the decrease in anterior pituitary DA content caused by haloperidol. The actions of acute and chronically administered haloperidol are reversible, with the reduced DA content of the adenohypophysis and the elevated serum concentrations of PRL returning to respective pretreatment levels in both young and aged rats once treatment stops. The time course for recovery of serum PRL levels and anterior pituitary DA contents after both the acute and chronic haloperidol treatment is of longer duration in the aged rat, which is consistent with a decreased rate of clearance of haloperidol in these animals. Twelve daily injections of bromocriptine, a DA agonist, reduced serum PRL and anterior pituitary DA concentrations in both young and aged rats, and these effects persisted for up to 7 days after the injections were stopped.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Prolactin-induced activation of tuberoinfundibular dopaminergic neurons: evidence for both a rapid 'tonic' and a delayed 'induction' component.

Results of previous studies have revealed that prolactin causes a delayed (12-16 h) increase in the rate of synthesis and turnover of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence. Attempts to demonstrate a rapid in vivo action of prolactin on these neurons has been frustrated because pharmacological manipulations needed to make the biochemical measurements of TIDA neuronal activity (i.e., administration of alpha-methyltyrosine or NSD 1015) inhibit DA synthesis and thereby remove the tonic inhibitory control of DA on prolactin secretion. Thus, 'control' rates of synthesis and turnover of DA in terminals of TIDA neurons are actually values obtained in the presence of high circulating concentrations of prolactin. Results of the present in vivo studies demonstrate that there are two components to the activation of TIDA neurons by prolactin: a rapid 'tonic' component, which is responsive to acute changes in prolactin concentrations, and a delayed 'induction' component, which is activated by long-term changes in prolactin concentrations. Experimental observations which support this proposal are described below. Hypophysectomy or treatment with bromocriptine (a DA agonist) reduce circulating levels of prolactin and reduce the rate of DA synthesis in the median eminence. Intracerebroventricular (i.c.v.) administration of prolactin to these animals increases the rate of DA synthesis in the median eminence within 4 h (rapid 'tonic' component) and then causes a further increase after 12 h (delayed 'induction' component); only the latter component is blocked by treatment with cycloheximide, indicating the involvement in protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term treatment with estradiol induces reversible alterations in tuberoinfundibular dopaminergic neurons: a decreased responsiveness to prolactin.

Previous studies have demonstrated that short-term (3-5 days) treatment with estradiol increases the rate of turnover and synthesis of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence by virtue of the ability of this hormone to increase circulating concentrations of prolactin. The present studies were undertaken to examine the long-term effects of estradiol on serum prolactin concentrations and TIDA neuronal activity (estimated by the rate of DOPA accumulation in the median eminence after the administration of a decarboxylase inhibitor). Female rats, ovariectomized for 2 weeks, were implanted subcutaneously with silastic capsules containing estradiol benzoate and sacrificed 6, 12 and 18 days after capsule implantation. Serum prolactin concentrations were markedly increased at 6, 12 and 18 days whereas the rate of DOPA accumulation was increased at 6 days but not at 12 days, and was decreased at 18 days. The concentration of DA in the median eminence was reduced at 6 days and further reduced at 12 and 18 days. The low rate of DOPA accumulation in the median eminence despite the high circulating concentrations of prolactin suggests that long-term estradiol treatment reduces the ability of TIDA neurons to respond to prolactin. This was confirmed by the finding that direct intracerebroventricular (icv) injections of prolactin increased the rate of DOPA accumulation in the median eminence of sham-implanted rats but not in 18 day estradiol-treated rats. To determine if the effects of estradiol were reversible, ovariectomized rats were implanted with estradiol-containing capsules for 18 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacological manipulation of anterior pituitary dopamine content in the male rat: relationship to serum prolactin concentration and lysosomal enzyme activity.

The content of dopamine (DA) and the activity of beta-glucuronidase (a marker for lysosomal enzymes) in the anterior pituitary and the concentration of PRL in serum were determined in male rats that were treated with a variety of drugs that influence the release, storage, or actions of DA. Drugs that increase DA in hypophysial portal blood (amphetamine, methylphenidate and L-dopa) increased DA content, decreased PRL secretion, and had no effect on lysosomal enzyme activity. Drugs that activate DA receptors in the anterior pituitary (apomorphine and bromocriptine) decreased serum PRL but had no effect on DA content or lysosomal enzyme activity. Drugs that decrease DA in the hypophysial portal blood (alpha-methyltyrosine, gamma-butyrolactone, and reserpine) or block DA receptors (haloperidol) increased PRL secretion and decreased DA content and lysosomal enzyme activity. These results suggest that there is no obvious relationship between anterior pituitary DA content and PRL secretion. In addition, lysosomal enzyme activity is not stimulated by increasing the concentration of DA or activating DA receptors in the anterior pituitary, but lysosomal enzyme activity does appear to be tonically stimulated by DA in the control animals since decreasing DA concentrations or receptor activation in the anterior pituitary decreases beta-glucuronidase activity. This latter proposal was confirmed by the demonstration that apomorphine reduced the alpha-methyltyrosine-induced increase in serum PRL and prevented the decrease in anterior pituitary DA content and beta-glucuronidase activity. Furthermore, pretreatment with bromocriptine and L-dopa blocked both the increase in serum PRL concentration and the decrease in anterior pituitary DA content induced by alpha-methyltyrosine and gamma-butyrolactone. On the other hand, bromocriptine and L-dopa blocked the increase in serum PRL concentration but not the reduction in anterior pituitary DA content caused by reserpine, indicating that reserpine has a direct action on DA storage mechanisms in the anterior pituitary. These data suggest that the ability of DA to inhibit PRL secretion and the incorporation of DA into the anterior pituitary are not causally related.

Animals↗

Adenohypophysial dopamine content during physiological changes in prolactin secretion.

Studies were undertaken to characterize the relationship between anterior pituitary dopamine (DA) content and changes in PRL secretion that occur during physiological states in which changes in tuberoinfundibular DA neuronal activity have been previously characterized. The results of these studies are summarized as follows. Serum PRL concentrations and the anterior pituitary DA content were not different between male and diestrous female rats, an unexpected result considering that tuberoinfundibular DA neuronal activity in female rats is 2- to 3-fold greater than that in male rats. The surge of PRL secretion during the afternoon of proestrus was accompanied by a significant decrease in the anterior pituitary content of DA. Increases in PRL secretion that occur early in pregnancy and during suckling were accompanied by a decrease in tuberoinfundibular DA neuronal activity and a decrease in the DA content in the anterior pituitary. Restraint stress increased PRL secretion and reduced the anterior pituitary DA content in both male and female rats, although only female rats respond to immobilization with a decrease in tuberoinfundibular DA neuronal activity. In both male and female aged rats, there were increases in serum PRL concentrations and the anterior pituitary DA content, despite the fact that tuberoinfundibular DA neuronal activity is reduced in the aged rat. Dehydration induced by water deprivation was associated with a small increase in serum PRL concentrations and a large increase in anterior pituitary DA content; similar water deprivation regimens have induced no change in indices of tuberoinfundibular DA neuronal activity. These results demonstrate that there is not a simple relationship among physiologically induced changes in PRL secretion, anterior pituitary DA content, and tuberoinfundibular DA neuronal activity. The results also indicate that the content of DA in the anterior pituitary cannot be used as a reliable index of tuberoinfundibular DA neuronal activity.

Aging↗

Dopaminergic neuronal function, anterior pituitary dopamine content, and serum concentrations of prolactin, luteinizing hormone and progesterone in the aged female rat.

The serum concentrations of prolactin (PRL), progesterone and luteinizing hormone (LH), and the content and rate of synthesis of dopamine (DA) in selected brain regions were determined in young (3-6 months), intermediate (13-15 months) and aged (24-25 months) female Long-Evans rats. Young rats were examined on the days of diestrus 2 and estrus. Intermediate rats were divided into 2 groups, a group which was cycling regularly (examined on the day of estrus) and a group which exhibited constant estrus. Aged rats were divided into 3 groups one which cycled regularly (examined on day of estrus), one which exhibited constant estrus, and one which exhibited repetitive pseudopregnancies. Serum PRL was increased in all intermediate and aged rats when compared to values in young animals. Serum LH was increased and progesterone decreased in those intermediate and aged rats which exhibited constant estrous reproductive patterns. The DA content was generally decreased in the median eminence, posterior pituitary, striatum, nucleus accumbens and olfactory tubercle of all aged rats, while the rate of DA synthesis was decreased only in the median eminence of aged, non-cycling rats. This suggests that all DA neuronal systems except those in the tuberoinfundibular system are able to compensate for the age-related loss. Despite the apparent reduction of tuberoinfundibular DA neuronal function the concentration of DA in the anterior pituitary, which is believed to represent amine released from the neurons, is dramatically increased in intermediate age rats in constant estrus, and in all groups of aged rats. The maintenance of high PRL secretion despite the elevated content of DNA in the anterior pituitary suggests an age-related defect in the dynamics of DA in this gland; this defect may contribute to the loss of reproductive function in the aging rat.

Aging↗

Temporal patterns of serum luteinizing hormone and testosterone and endocrine response to luteinizing hormone releasing hormone in aging male rats.

Temporal patterns of serum testosterone and luteinizing hormone (LH) concentration and responsiveness to luteinizing hormone releasing hormone (LHRH) were measured in young (2 to 3 months), middle-aged (12 to 13 months), and aged (22 to 26 months) male rats. Average testosterone and LH concentrations, as well as individual sample variations, were higher in young than in middle-aged and aged rats and higher in middle-aged than in aged groups. In addition, the young group showed a diurnal pattern of serum testosterone concentration and greater ranges of LH and testosterone concentrations in individual blood samples. Young male rats showed greater increases in serum LH and testosterone than middle-aged and aged groups after intravenous LHRH, 1 and 5 ng/g of body weight. These data indicate that LH and testosterone secretion are progressively reduced in the aged male rat and suggest alterations in neuroendocrine control of pituitary gonadotropin secretion as the most important alteration in the gonadal control system in these animals.

Aging↗