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PubMed2000

Macroprolactinemia in childhood and adolescence: a cause of asymptomatic hyperprolactinemia.

Asymptomatic hyperprolactinemias associated with altered proportions of molecular forms of circulating prolactin (PRL) have been reported in adults. The scarce references available in children and adolescents prompted us to report our experience in the evaluation and follow-up of patients with macroprolactinemia. We studied 5 patients (1 male and 4 females) aged 11.6-18 years with incidentally discovered asymptomatic hyperprolactinemia. Patients underwent repeated evaluations for a period of 3 months to 8 years, and their PRL levels remained elevated (34.4-516 ng/ml). Structural variants of PRL >/=45 kD ranged between 58.9 and 78.6%. Chromatographic profiles showed increases in Big Big PRL in the 5 cases, ranging between 40 and 72% (normal: 9-21%), and in Big PRL in 3 cases, ranging between 30.0 and 32.6% (normal: 5-25%). Little PRL was decreased in all cases, ranging between 20.6 and 41.1% (normal: 50-90%). In conclusion, upon detection of hyperprolactinemia with no clinical manifestations and no alteration of the remaining endocrine functions, macroprolactinemia should be considered as a possible diagnosis. The confirmed absence of functional alterations during the follow-up would favor a no-treatment approach and at the same time avoid repeating imaging studies.

Adolescent↗

PubMed1985

Menstrual disorders associated with hyperprolactinemia.

In hyperprolactinemia, menstrual disorders ranging from irregular bleeding, insufficient luteal phase, spanio-amenorrhea, to anovulatory cycles and amenorrhea, are frequent. Multiple mechanisms are involved in these disorders: hyperprolactinemia could act at the hypothalamic level on LHRH secretion and directly on LH and sex steroids secretion. Hyperprolactinemia could also act by impairing fertilization or implantation at the endometrial level.

Female↗

PubMed1995

Verapamil-induced hyperprolactinemia complicated by a pituitary incidentaloma.

OBJECTIVE: To describe a patient with an incidental pituitary lesion who experienced verapamil-induced hyperprolactinemia. CASE SUMMARY: A patient experiencing impotence was found to have increased prolactin and low testosterone concentrations. Verapamil as a cause for his increased prolactin concentration was not considered initially. The patient underwent extensive testing to rule out a pituitary tumor. Magnetic resonance imaging showed a 6-mm lesion consistent with a pituitary microadenoma that had remained unchanged for 6 months. Verapamil therapy was discontinued and within 1 month the patient's prolactin concentration decreased from 46.8 to 14.4 micrograms/L, and has remained within normal limits. DISCUSSION: We reviewed reports of verapamil-induced hyperprolactinemia. This case was unique as this patient had an incidental pituitary lesion that was not responsible for increasing the prolactin concentration in our patient, but rather complicated the identification of a drug-induced disorder. CONCLUSION: The failure to identify the hyperprolactinemic effect of verapamil may have resulted in performing unnecessary radiologic procedures in this patient. This case highlights the importance of obtaining a medication history in patients with hyperprolactinemia.

Aged↗

PubMed1987

The effect of hyperprolactinemia produced by transplantable pituitary MtTW15 tumor cells in male rats on hypothalamic luteinizing hormone-releasing hormone release in vitro: effects of naloxone and K+.

Although hyperprolactinemia has been reported to decrease reproductive function in male rats, the mechanism of these effects is not fully understood. We examined the effects of chronic hyperprolactinemia and castration on the LHRH content of the medial basal hypothalamus (MBH) and on the basal and evoked in vitro release of LHRH from the MBH-preoptic area (POA). Adult Wistar-Furth male rats were inoculated with MtTW15 tumor fragments; 3 weeks later half of the rats were castrated. Hyperprolactinemic (H) and normoprolactinemic (N) rats were decapitated 2 weeks later to measure MBH LHRH and serum PRL and LH levels. Elevated PRL levels (greater than 2 micrograms/ml) resulted in significantly increased MBH LHRH stores. Castration caused a 57% depletion of MBH LHRH in N rats; in castrated H rats the MBH LHRH content was also reduced by 40%, a significantly lesser extent. Although serum LH levels in intact H rats were only slightly reduced, postcastration LH hypersecretion was significantly attenuated. In a parallel study, the LHRH release rate was assessed by in vitro perfusion of the MBH-POA. The basal LHRH release rates of intact N and H rats were similar. Castrated N rats released LHRH at a reduced rate (50%; P less than 0.01), whereas in castrated H rats the LHRH release rate was reduced by 20%, which corresponded with the partial depletion of the MBH LHRH content in these rats. To examine the possibility of opiate involvement, LHRH release evoked by two consecutive naloxone (NAL) infusions (1 mg/ml for 30 min) was studied. The two NAL infusions resulted in two similar significant increments of LHRH in the MBH-POA of intact N and H rats. However, castration produced different effects on the NAL-induced LHRH release. First, the second NAL pulse was not effective in stimulating LHRH release from the MBH-POA of N and H castrated rats. Further, the first NAL infusion elicited a significant increase in LHRH output from the MBH-POA of N and H castrated rats, but it was significantly lower in comparison with that in their respective intact counterparts. In addition, the NAL-induced LHRH response was higher from the MBH-POA of castrated H than that in castrated N rats. These studies show that neither basal nor evoked LHRH output in vitro is affected by severe and chronic hyperprolactinemia produced by MtTW15 pituitary tumor cells in intact male rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Hyperprolactinemia increases and hypoprolactinemia decreases tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nuclei, but not the substantia nigra or zona incerta.

The effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase (TH) mRNA signal levels were examined in dopaminergic neurons ovariectomized rats. TH mRNA signal levels and relative TH quantity in the arcuate nuclei, zona incerta, and substantia nigra were evaluated by in situ hybridization and immunocytochemistry, respectively. The catalytic activity of TH in the stalk-median eminence (SME) was determined from the in vitro rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine. Chronic administration of bromocriptine (BROMO), a dopamine (DA) agonist, for 3 days reduced circulating rat PRL (rPRL) levels compared to those in the vehicle-treated controls. BROMO treatment decreased TH mRNA signal levels in the arcuate nuclei, the intensity of TH immunostaining in the arcuate-median eminence area, and the rate of DOPA accumulation in the SME. Concomitant administration of ovine PRL (oPRL) reversed the effects of BROMO on TH, resulting in markedly increased TH mRNA signal levels, intensity of TH immunostaining, and rate of DOPA accumulation. Treatment with oPRL by itself for 3 days increased TH mRNA signal levels in the arcuate nuclei and TH activity in the SME, compared to vehicle. Chronic treatment with haloperidol, a DA antagonist, increased circulating levels of endogenous rPRL and increased TH activity in the SME to values similar to those after oPRL treatment. However, in contrast to oPRL, mRNA levels in the arcuate nuclei of haloperidol-treated rats were similar to levels in vehicle-treated animals. To evaluate whether the effect of PRL on TH was species specific, oPRL or rPRL was continuously infused into the jugular vein using an osmotic minipump. TH mRNA levels in the arcuate nuclei were elevated above control levels by either oPRL or rPRL administration. TH mRNA levels in the DA perikarya located in the zona incerta and substantia nigra were not altered by treatment with a DA agonist, a DA antagonist, or PRL. These results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment, respectively, TH mRNA levels in the tuberoinfundibular dopaminergic neurons. The alterations in TH mRNA content probably contribute to the decrease or increase in TH activity associated with hypoprolactinemia or hyperprolactinemia, respectively.

Animals↗

PubMed1988

Pathological hyperprolactinemia suppresses hot flashes in menopausal women.

Hyperprolactinemia impairs pituitary-gonadal function in young women, but its effect in menopausal women is not known. The purpose of this report is to describe the effect of hyperprolactinemia on gonadotropin secretion and hot flashes in menopausal women before and after treatment with a dopamine agonist. We studied two such women with prolactinomas. Both had plasma LH and FSH levels in the range found in premenopausal women and no hot flashes. Treatment with bromocriptine was associated with normalization of plasma PRL levels, elevation of plasma gonadotropin levels, and the onset of menopausal hot flashes in both patients. We conclude that hyperprolactinemia can inhibit the augmented gonadotropin secretion that occurs in postmenopausal women and prevent hot flashes.

Adenoma↗

PubMed1991

A comparison of the efficacy and safety of pergolide and bromocriptine in the treatment of hyperprolactinemia.

UNLABELLED: Pergolide is a synthetic ergoline derivative with highly potent long-acting PRL-lowering activity, allowing therapy of hyperprolactinemia with a once daily administration of the drug. The results of two open-label, randomized controlled multicenter clinical trials are reported. Pergolide (taken once a day), was compared with bromocriptine (taken two to four times daily) regarding efficacy and safety in the reduction of PRL levels, the cessation of galactorrhea and amenorrhea, the improvement in sexual function, and tumor shrinkage in hyperprolactinemia without (trial I; 61 patients) and with radiologically evident pituitary tumors (trial II; 96 patients). Both drugs were equally effective in lowering PRL levels in both trials. A median optimal dose of 50 micrograms pergolide and 5 mg bromocriptine/day suppressed PRL levels in the 61 patients of trial I by more than 80%. During the 24-week investigational period galactorrhea disappeared in 96% and 87% of patients, whereas menstruation returned in 90% and 96% of patients, respectively. An equally high efficacy (optimal median dose: 75-100 micrograms pergolide, 7.5-10 mg bromocriptine daily) was observed in trial II, although the resumption of menses was less frequent than in the patients of trial I (50% and 58% of patients, respectively). Sexual dysfunction improved similarly on both drugs in about half the patients. In addition, tumor shrinkage occurred to a similar extent with both drugs. A high incidence of adverse events was noted especially at the initiation of therapy with both compounds: nausea, dizziness, vomiting, asthenia, headache, and decrease in blood pressure occurred at a similar incidence and extent during the use of pergolide and bromocriptine. Patients in trial I treated with pergolide reported a slightly higher incidence of fever, vasodilatation, and flu syndrome. CONCLUSIONS: in these 24-week studies comprising a total of 157 hyperprolactinemic patients, a once daily administration of pergolide was shown to be as safe and effective as the two to four times daily ingestion of bromocriptine. Longer-acting dopamine agonists like pergolide that can be taken once daily, are likely to increase the ease to adherence to the therapeutic regimen. This might result in a higher compliance to medical treatment of hyperprolactinemia.

Adult↗

PubMed1992

A longitudinal analysis of premenopausal bone loss in healthy women and women with hyperprolactinemia.

In this report we describe longitudinal measurements of forearm and spinal bone mineral in healthy women and women with hyperprolactinemia. One hundred and ten women underwent yearly assessment of forearm and spinal bone mineral by single photon absorptiometry and computed tomography for an average of 4.7 yr. At entry into the study, women with hyperprolactinemic amenorrhea had 21% lower spinal bone mineral and 2.5% lower forearm bone mineral than healthy premenopausal women. Despite decreased estradiol levels (31 +/- 23 pmol/L), spinal bone in women with hyperprolactinemic amenorrhea did not change over time (+0.08%/yr; P = 0.89). In contrast, spinal bone in healthy women with regular menses (mean age, 34.6 +/- 6.6 yr) decreased significantly (1.7%/yr; P = 0.01). Cortical bone in the forearm did not change in either group. The hyperprolactinemic subjects had higher body mass index (28 +/- 6 vs. 24 +/- 4 kg/m2) and serum testosterone (0.5 +/- 0.2 vs. 0.39 +/- 0.16 pmol/L) than control subjects, but neither parameter correlated with bone loss. Although 64% of the hyperprolactinemic subjects had serum estradiol levels below 30 pmol/L, there was no correlation between estradiol or duration of amenorrhea and bone loss. Women with normal PRL levels and regular menses 3-9 yr after treatment of hyperprolactinemia had significantly lower spinal bone mineral (147 +/- 28 mg/mL) than healthy premenopausal women (169 +/- 29 mg/mL) and showed no change in spinal bone (+0.3%/yr; P = 0.67) over 5 yr. Despite significant hypoestrogenemia, women with hyperprolactinemic amenorrhea did not evidence a rapid decline in spinal bone. Restoration of gonadal function was not associated with normalization of bone mineral. The bone loss that accompanies hyperprolactinemia is not comparable to that which occurs after oophorectomy or menopause. These findings raise important questions about the importance of osteopenia as an indication for treatment of hyperprolactinemic amenorrhea.

Adult↗

PubMed1992

Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia.

We have demonstrated the presence of anti-PRL autoantibody in 5 patients with idiopathic hyperprolactinemia. The clinical features were suggestive of a weak biological activity of PRL, such as regular menses and no galactorrhea. Total PRL levels were markedly elevated (685 +/- 386 micrograms/L) (mean +/- SD) and the proportion of the bound form was 90.7 +/- 7.1%. Scatchard analysis revealed a low-affinity, high-capacity antibody: the association constant was 0.73 +/- 0.56 x 10(7) mol-1 and the maximal binding capacity was 2139 +/- 1792 micrograms/L. Gel filtration study showed that a substantial amount of PRL (64.6 +/- 19.5%) was eluted at the position of 150,000-170,000 mol wt PRL (big-big PRL). Immunoprecipitation study using the chain-specific antibodies showed that the anti-PRL autoantibody belonged to kappa-type immunoglobulin G. These results may indicate that there exists autoantibody-related hyperprolactinemia, especially in those with particularly high serum PRL levels, who had previously been diagnosed as "idiopathic" hyperprolactinemia.

Adult↗

PubMed1995

Hyperprolactinemia caused by lactation and pituitary adenomas is associated with altered serum calcium, phosphate, parathyroid hormone (PTH), and PTH-related peptide levels.

PRL stimulates systemic release of PTH-related peptide (PTHrP) in animals. To determine whether hyperprolactinemia causes PTHrP release in humans, we studied the relationship between PRL and PTHrP in lactating women and patients with PRL-producing pituitary adenomas. Thirty-three lactating women and 16 patients with pituitary adenomas were paired with healthy age- and sex-matched controls. Serum total calcium, albumin, phosphate, PRL, intact PTH, and PTHrP were measured. Mean calcium and phosphate levels were higher in lactating women than in control subjects [2.39 +/- 0.01 vs. 2.35 +/- 0.01 mmol/L (P < 0.01) and 1.33 +/- 0.03 vs. 1.13 +/- 0.02 mmol/L (P << 0.001), respectively]. Mean PTH was lower (2.49 +/- 0.24 vs. 3.17 +/- 0.23 pmol/L; P < 0.04) and mean PTHrP was higher than control values (0.93 + 0.08 vs. 0.38 +/- 0.04 pmol/L; P << 0.001). PRL correlated negatively with PTH (P < 0.02) and positively with PTHrP (P < 0.05). Mean calcium, phosphate, and PTH levels were not different between patients with pituitary adenomas and control subjects. The mean PTHrP level was higher in patients with pituitary adenomas (0.75 +/- 0.10 vs. 0.39 +/- 0.07 pmol/L; P < 0.006) and fell significantly with therapy to normalize PRL (P < 0.03). We conclude that PTHrP levels are increased in hyperprolactinemia caused by lactation and pituitary adenomas. In lactating women, the increased PTHrP was associated with higher mean calcium and phosphate and lower PTH levels. The metabolic consequences of these abnormalities in hyperprolactinemia require further elucidation.

Adenoma↗

PubMed2006

Drug-induced hyperprolactinemia.

Hyperprolactinemia is the most common biochemical abnormality currently encountered in clinical endocrinology. Hyperprolactinemic syndromes are a diverse group of disorders that are common in both men and women. Once the diagnosis of hyperprolactinemia has been established, the patient should be screened for the numerous causes of hormone hypersecretion. Hence, an accurate medical history is extremely important for the clinician to find out the most frequent causes of hypersecretion of prolactin (e.g., drugs). Clinicians should be aware of the possibility of prolactin elevation and associated problems with any drug that has the potential to cause hyperprolactinemia, particularly in patients who have other factors that might stimulate prolactin release.

Drug-Related Side Effects and Adverse Reactions↗

PubMedDate not supplied

Hyperprolactinemia in men: clinical and biochemical features and response to treatment.

Hyperprolactinemia induces hypogonadism by inhibiting gonadotropin-releasing hormone pulsatile secretion and, consequently, follicle-stimulating hormone, luteinizing hormone, and testosterone pulsatility. This leads to spermatogenic arrest, impaired motility, and sperm quality and results in morphologic alterations of the testes similar to those observed in prepubertal testes. Men with hyperprolactinemia present more frequently with a macroadenoma than a microadenoma. Symptoms directly related to hypogonadism are prevalent. In men hypogonadism leads to impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia. It is present in 16% of patients with erectile dysfunction and in approx 11% of men with oligospermia. Treatment with bromocriptine or cabergoline (CAB) is effective in men with prolactinomas, with a response that is in general comparable to treatment in women. Seminal fluid abnormalities rapidly improve with CAB treatment, while other dopaminergic compounds require longer periods of treatment. Moreover, to improve gonadal function in men, the integrity of the hypothalamic-pituitary-gonadal axis is necessary. New promising data indicate that a substantial proportion of patients with either micro- or macroprolactinoma do not present hyperprolactinemia after long-term withdrawal from CAB. Whether this corresponds to a definitive cure is still unknown, but treatment withdrawal should be attempted in patients achieving normalization of prolactin levels and disappearance of tumor mass to investigate this issue.

Humans↗

PubMed1986

[Effects of transient or occult hyperprolactinemia on luteal function].

It is well known that the luteal function in the patients with hyperprolactinemia is much suppressed by high level of serum prolactin. Present study was performed to investigate whether the luteal function in the patients with transient or occulted hyperprolactinemia was affected by the transient increase of serum prolactin level. The circadian changes of serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were examined in seven cases of the transient or occulted hyperprolactinemia whose BBT charts showed biphasic patterns. Serum prolactin levels of these patients were less than 25 ng/ml at daytime and more than 150 ng/ml at 30 minutes after the administration of 500 micrograms of TRH. Blood samplings were taken every two hours through an intravenous indwelling catheter without any disturbances. All of the patients had their breakfast at 7 to 8, lunch at 11 to 12 and dinner at 17 to 18 o'clock and slept from 22 until 6 in the next morning. Serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were determined by RIA and the circadian changes of these hormones were analysed. Then, 5 mg of bromocriptine was administered every day to these patients for more than 30 days and the duration of the luteal phase and the mid-luteal serum estradiol and progesterone levels for the indicators of the luteal function were examined before and after the administration of bromocriptine. The circadian changes of serum prolactin levels in the patients showed significant increase during both daytime and night compared to those of the control (p less than 0.005, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Inhibition of human chorionic gonadotropin-induced ovulation and steroidogenesis by short-term hyperprolactinemia in female rabbits.

To clarify the possible direct effects of hyperprolactinemia on the ovulatory process, we experimentally established hyperprolactinemia in female rabbits with 4 daily injections of sulpiride (SLP) at different doses and induced ovulation with human chorionic gonadotropin (hCG). Plasma levels of prolactin (PRL) were increased significantly before hCG injection in each SLP-treated group compared with the corresponding values for the controls. The ovulation rates at 14 h after hCG were significantly reduced in the 16 and 24 mg/kg/day SLP-treated groups. An inverse correlation (r = -0.74, P less than 0.001) was found between the ovulation rate and the increasing in plasma PRL measured just prior to hCG injection. The increase in peripheral as well as ovarian venous progesterone and 20 alpha-hydroxypregn-4-en-3-one(20 alpha-OHP) at 4 and 14 h after hCG injection in inhibited ovulation groups was much less than in the control group. However, the estradiol, androstenedione and testosterone concentrations were comparable with the control values. These results indicate that hypersecretion of PRL induced by SLP has a direct effect on ovary by inhibiting follicular rupture induced by hCG and this inhibitory effect was partly due to the suppression of progesterone secretion during the course of ovulation. This may be one of the causes leading to hypogonadism during hyperprolactinemia.

Animals↗

PubMed1991

Paradoxical prolactin response to growth hormone-releasing hormone in a patient with hyperprolactinemia and empty sella.

In a 30-year-old woman with amenorrhea due to hyperprolactinemia, serum PRL increased to twice the basal amount in response to growth hormone-releasing hormone (GHRH). Roentgenological studies revealed no pituitary adenoma but empty sella. Bromocriptine therapy normalized serum PRL and made the paradoxical response to GHRH disappear. The paradoxical response did not occur in any of eight other patients with hyperprolactinemia due to prolactinoma. Although this case is rare, GHRH stimulates PRL as well as GH release remarkably in some cases with hyperprolactinemia without a GH-producing tumor.

Adult↗

PubMed1992

Hyperprolactinemia and macrocytosis in women with alcohol and polysubstance dependence.

Chronic alcoholism and drug abuse are often associated in women with derangements of reproductive function such as amenorrhea, anovulation, luteal phase dysfunction and early menopause. Endocrine profiles were studied of the first 18 women (aged 17-58) admitted consecutively to a Massachusetts hospital for treatment of alcohol/polysubstance dependence under civil commitment. Twelve women were diagnosed as alcohol dependent according to criteria established in DSM-III-R. Their daily alcohol consumption ranged from 42-324 grams. Six women were diagnosed as polysubstance dependent. In addition to alcohol (84-831 g/day), cocaine was the most frequently abused drug followed by tranquilizers, marijuana and opiates. Over 60% of alcohol-dependent women of reproductive age had either hyperprolactinemia or macrocytosis (increased mean corpuscular volume, MCV), or both. Over 60% of the polysubstance-dependent women of reproductive age had either hyperprolactinemia or increased MCV. Over 80% of alcohol-dependent women of postmenopausal age had either hyperprolactinemia or increased MCV, or both. We conclude that evaluation of plasma prolactin levels and MCV may be useful as biological state markers for alcoholism and polysubstance abuse in women.

Adolescent↗

PubMed1986

Modulation of ovarian LH receptor and serum hormone levels in rats with hyperprolactinemia induced by administration of ovine prolactin or sulpiride.

Hyperprolactinemia was experimentally produced in rats by administration of ovine prolactin (oPRL) and sulpiride, and tried to evaluate the effect of hyperprolactinemia on ovarian receptor for luteinizing hormone (LH) as well as that on serum gonadotropin and steroid hormone levels. Wistar-Imamichi strain mature female rats showing 4-day estrous cycles were treated with various doses of oPRL or sulpiride twice a day for 4 days from diestrus. They were killed on the fifth day. Binding of ovarian LH receptors was reduced by a small dose of oPRL (0.1 IU) or sulpiride (0.25 mg) and restored to normal by larger doses of oPRL. However, larger doses of sulpiride (50 or 100 mg) increased the receptor bindings beyond the control level (4.39 +/- 0.40 ng/mg homogenate protein). Serum prolactin levels decreased in rats treated with larger doses of oPRL, but increased with larger doses of sulpiride. Serum LH levels increased with both agents. Although the ovaries treated with either oPRL or sulpiride suggested the lack of ovulation, there were no significant changes of steroid hormones in oPRL groups. In contrast, sulpiride treatment resulted in a reduction of estradiol and an increase of progesterone secretion, suggesting the prolonged effect of the drug. Thus, prolactin appeared to act on the rat ovarian LH receptors in two different manners in hyperprolactinemia, depending on the amount of this hormone or a ratio of prolactin to LH.

Animals↗

PubMed2002

Stimulatory effects of hyperprolactinemia on aldosterone secretion in ovariectomized rats.

BACKGROUND: To evaluate the effects of hyperprolactinemia on aldosterone secretion and its mechanisms of action in ovariectomized (OVX) rats. METHODS: Hyperprolactinemia was induced by the transplantation of rat anterior pituitary (AP) glands under the kidney capsule for 6 weeks in female rats. Control rats underwent cerebral cortex (CX) transplantation. Four weeks after transplantation, the rats were OVX 2 weeks before decapitation. After decapitation, the trunk blood was collected, and the adrenal glands of CX- and AP-grafted rats were prepared as zona glomerulosa (ZG) cells for in vitro study. RESULTS: Plasma prolactin and aldosterone in the rats were increased by AP gland transplantation. In the in vitro study, the basal aldosterone secretion by the adrenal ZG cells was higher in AP-grafted rats than in CX-grafted rats. The AP-grafted group showed increased responsiveness to angiotensin II (10(-8) M), KCl (8 x 10(-3) M), or 8-bromo-adenosine 3',5'-cyclic monophosphate (8-br-cAMP; 10(-4) M, a membrane-permeable analogue of cAMP) with regard to aldosterone secretion as compared with the CX-grafted group. N-(2-[p-Bromocinnamylamine]ethyl)-5-isoquinolinesulfonamide (H89; 10(-6), 10(-5) M, a protein kinase A inhibitor) or tetrandrine (10(-5) M, a blocker for both L-type and T-type Ca2+ channels) induced a greater suppression of aldosterone secretion in the AP-grafted group than in the CX-grafted group. No significant differences between the CX- and AP-grafted groups were observed, however, with regard to the adrenocorticotropichormone (10(-9) M)-, forskolin (10(-5) M, an adenylyl cyclase activator)-, or nifedipine (10(-5) M, an L-type Ca2+ channel blocker)-induced responsiveness of aldosterone secretion. In addition, there was no difference in the expression of desmolase (i.e., cytochrome P450 side-chain cleavage enzyme) in ZG cells between AP- and CX-grafted rats. The conversions of 25-OH-cholesterol into pregnenolone in the presence of trilostane (an inhibitor of 3beta-hydroxysteroid dehydrogenase) and corticosterone into aldosterone, as well as the expression of the steroidogenic acute regulatory protein in ZG cells, were greater in AP-grafted rats than in CX-grafted rats. CONCLUSIONS: These results suggest that hyperprolactinemia increases basal, angiotensin II- and KCl-stimulated aldosterone secretion by ZG cells in OVX rats through activation of T-type Ca2+ channels, the post-cAMP and protein kinase A pathway, cytochrome P450 side-chain cleavage enzyme, and aldosterone synthase, as well as by causing increased expression of steroidogenic acute regulatory protein in ZG cells.

8-Bromo Cyclic Adenosine Monophosphate↗