Biomedical subjects

W B Malarkey

Publications and source records attributed to W B Malarkey.

At least 73 records · Page 4Linked to original sources

PubMed1987

Sequential prolactin evaluation of a "cured" patient with recurrence of prolactinoma.

Several investigators have suggested that prolactin secretion in some subjects with hyperprolactinemia associated with pituitary macroadenomas may have a resistance to the prolactin inhibitory hormone, dopamine. This report describes a male subject with a prolactinoma whose preoperative evaluation demonstrated a resistance of prolactin release to inhibition by dopamine. Evaluation of prolactin secretion from monolayer culture of his tumor also revealed a resistance to inhibition by dopamine. Four months postoperatively, normal serum prolactin levels and a normal maximal inhibition of prolactin to a dopamine infusion of 0.04 microgram/kg/minute suggested surgical cure. However, a 24-hour prolactin sampling revealed blunted nocturnal augmentation of prolactin release, an early escape of inhibition of prolactin release at 150 minutes from a 0.04 microgram/kg/minute dopamine infusion, and abnormal prolactin response to a low-dose (0.004 microgram/kg/minute) dopamine infusion. Hence, persistent abnormalities in prolactin secretory dynamics were noted with more extensive testing in this patient when he was thought to have been cured. One year postoperatively, the hyperprolactinemia recurred, prolactin release was markedly resistant to dopamine, and an abnormal 24-hour prolactin profile of release was present. Thus, resistance of prolactin secretion to inhibition by dopamine was present in this patient with a prolactinoma. Additionally, an abnormal prolactin response to dopamine was noted to precede the development of hyperprolactinemia with tumor recurrence.

Adenoma↗

PubMed1987

Patients with primary hypothyroidism presenting as prolactinomas.

Hyperprolactinemia can occur in patients with primary hypothyroidism. Two women with hypothyroidism who had elevated serum prolactin levels, galactorrhea, amenorrhea, and pituitary computed tomographic scans that demonstrated the presence of "pituitary tumors" were recently evaluated. It was believed that they had prolactinomas, and they were referred for possible surgery. An elevated serum thyroid-stimulating hormone level, however, suggested that they had primary hypothyroidism and probably pituitary enlargement secondary to pituitary hyperplasia. Detailed evaluation of thyroid-stimulating hormone and prolactin secretion was performed. These studies revealed several abnormalities in dopamine-prolactin interactions; however, the primary event responsible for the hyperprolactinemia is unclear. These women were given thyroxine therapy, and subsequent radiologic and endocrine studies documented resolution of their "pseudotumors" and normalization of the serum thyroxine and prolactin levels. Hence, thyroid-stimulating hormone levels should be measured in all patients presenting with a suspected prolactinoma so that any hypothyroidism that is noted is not presumed to be due to secondary hypothyroidism from tumor involvement of the pituitary.

Adult↗

PubMed1987

Acute effects of exercise on plasma catecholamines in sedentary and athletic women with normal and abnormal menses.

Norepinephrine plays a role in the regulation of luteinizing hormone secretion and may therefore be involved in the etiology of exercise-induced menstrual dysfunction. This study evaluated both intraexercise and postexercise responses of epinephrine, norepinephrine, and dopamine in sedentary women and women runners with normal and abnormal menstruation. Five eumenorrheic nonrunners and five eumenorrheic, four oligomenorrheic, and five amenorrheic runners were evaluated on 2 consecutive days. On day 1, the women cycled on a bicycle ergometer against an increasing work load until exhaustion, and on day 2, the women underwent a submaximal exercise regimen. Serial blood draws were taken at specified time intervals during intraexercise and postexercise periods on both days. The data collected during exercise for all groups showed that epinephrine and norepinephrine had a sixfold to sevenfold rise on day 1 and had a threefold rise on day 2. Dopamine increased twofold during both exercise protocols. On day 1 norepinephrine displayed a significantly higher percentage change from baseline to peak levels for oligomenorrheic and amenorrheic runners than for eumenorrheic runners and sedentary women. This latter finding is consistent with the hypothesis that periodic marked elevations in norepinephrine levels during maximal exercise may interfere with pulsatile luteinizing hormone release and hence may play a role in the occurrence of menstrual dysfunction in women runners.

Adult↗

PubMed1987

Angiotensin II promotes prolactin release from normal human anterior pituitary cell cultures in a calcium-dependent manner.

Renin and angiotensin II (AII) have been demonstrated in the mammalian central nervous system, and AII has been found to promote PRL release in the rat and monkey. We added AII to monolayer cultures of human anterior pituitary cells and found significant PRL release by 30 min with concentrations of AII as low as 10(-10) M. This AII-induced PRL release was inhibited by the specific AII antagonist saralasin. AII-induced PRL release was a calcium-dependent process, since the calcium channel blockers verapamil and nifedipine as well as the calcium-calmodulin antagonist R2471 significantly inhibited AII-induced PRL release. Prostaglandins E2, A2, and F2 alpha also inhibited AII-induced PRL release. The significance of this latter observation is not clear, however, as indomethacin, an inhibitor of the cyclo-oxygenase prostaglandin metabolic pathway, had no effect on AII-induced PRL release. In light of recent immunohistochemical evidence of the presence of renin, angiotensinogen, and converting enzyme in human lactotrophs, our data support the concept that AII may be an important autocrine regulator of PRL secretion.

Adult↗

PubMed1986

The acute effects of exercise on prolactin and growth hormone secretion: comparison between sedentary women and women runners with normal and abnormal menstrual cycles.

Acute exercise may stimulate PRL secretion, which, in turn, may contribute to exercise-associated menstrual dysfunction. We compared the response of PRL secretion in sedentary women and women runners with normal and abnormal menstrual cycles. We also studied the GH response to acute exercise, as GH may bind to lactogenic receptors. Five nonrunning women, 5 eumenorrheic running women, four oligomenorrheic running women, and six amenorrheic running women were studied on 2 consecutive days. On day 1, the women cycled on a bicycle ergometer against an increasing workload until total exhaustion. Serum PRL and GH increased several-fold in response to acute exercise in all three groups of running women. On day 2, the women simulated a daily training run by enduring a designed submaximal exercise regimen. In response to submaximal exercise, no group had a significant elevation of PRL or GH. Therefore, a threshold of exercise intensity exists that must be achieved before a significant increase in PRL or GH secretion occurs in women runners; serum PRL and GH in the nonrunning group did not increase significantly even in response to acute maximal exercise. The transient elevations in PRL and GH in women runners probably do not contribute to their menstrual dysfunction unless individual hypersensitivity of the hypothalamic-pituitary-ovarian axis to such intermittent elevations is present.

Adult↗

PubMed1985

Weight loss in amateur wrestlers and its effect on serum testosterone levels.

Levels of nine serum hormones, six skin-fold sites, and body weight were measured in 19 male amateur wrestlers during their competitive season and again two months after the season. Percent of body fat was estimated from skin-fold thicknesses. Body weight, body fat, testosterone level, and prolactin level were significantly lower during the wrestling season. Low serum testosterone levels were significantly correlated with low body fat, large loss of body fat, and large weight loss. These findings suggest that the dietary restriction practiced by some wrestlers may affect serum testosterone levels adversely.

Adipose Tissue↗

PubMed1985

Vasoactive intestinal peptide effects on GH3 pituitary tumor cells: high affinity binding, affinity labeling, and adenylate cyclase stimulation. Comparison with peptide histidine isoleucine and growth hormone-releasing factor.

The vasoactive intestinal polypeptide (VIP) receptor was characterized on the GH3 rat pituitary tumor cell line using competitive binding studies with peptides having sequence homology with VIP. Further studies investigated receptor coupling to the adenylate cyclase complex by measurement of cAMP levels. Finally, the molecular weight of the receptor was estimated by affinity labeling techniques. Studies using 125I-VIP and unlabeled competing peptides revealed a single class of high affinity binding sites with a dissociation constant (KD) of 17 +/- 2 nM (mean +/- S.E.M.) for VIP, 275 +/- 46 nM for peptide histidine isoleucine (PHI), and 1380 +/- 800 nM for human pancreatic growth hormone releasing factor (GHRF). VIP and PHI each stimulated intracellular cAMP accumulation in a dose-dependent manner; both peptides demonstrated synergism with forskolin. In contrast, GHRF neither stimulated accumulation of cAMP nor demonstrated synergism with forskolin. VIP plus PHI (1 microM each) caused no significant increase in cAMP over either VIP or PHI alone, implying that the two peptides act through the same receptor. Covalent crosslinking of 125I-VIP to its binding site using either disuccinimidyl suberate (DSS) or ethylene glycol bis(succinimidyl succinate) (EGS) was followed by SDS-PAGE and autoradiography. The result is consistent with an Mr 47 000 VIP-binding subunit comprising or being associated with the VIP receptor of GH3 pituitary tumor cells.

Adenylyl Cyclases↗

PubMed1985

Physiologic concentrations of dopamine fail to suppress prolactin secretion in patients with idiopathic hyperprolactinemia or prolactinomas.

Several investigators have suggested that normal responsiveness to dopamine is exhibited by pituitary lactotrophs in patients with idiopathic hyperprolactinemia and prolactinomas. These studies, however, have employed dopamine infusion rates that produced supraphysiologic serum dopamine concentrations. In order to further examine this issue, we infused graded doses of dopamine to normal men and women as well as to patients with idiopathic hyperprolactinemia and prolactinomas. Dopamine infusion rates as low as 0.004 micrograms/kg/min, which were associated with physiologic serum dopamine levels, produced significant (p less than 0.01) suppression of prolactin in normal women and in normal males (p less than 0.05). In contrast, a 10-fold increase in the dopamine infusion rate, 0.04 micrograms/kg/min, was required in the hyperprolactinemic subjects to produce prolactin suppression similar to that found in the control subjects. Hence, prolactin secretion in both tumors and other hyperprolactinemic states is associated with a resistance to suppression by dopamine.

Adolescent↗

PubMed1985

Macroprolactinemia presenting like a pituitary tumor.

A serum prolactin level greater than 200 ng/ml is almost pathognomonic of a pituitary tumor in a nonpregnant woman. A patient with a three-year history of documented serum prolactin levels of 350 to 400 ng/ml and no evidence of a pituitary adenoma on computed axial tomographic scanning was recently studied. Detailed evaluation included a 24-hour prolactin profile that revealed blunting of the nocturnal augmentation of prolactin release, low-dose dopamine infusion resulting in normal inhibition of prolactin secretion, and a thyrotropin-releasing hormone bolus that showed a blunted stimulation of prolactin release. Analysis of circulating prolactin by column chromatography of her serum revealed that greater than 85 percent of her circulating immunoreactive prolactin had a molecular weight greater than 100,000 daltons (macroprolactin). This contrasts with other hyperprolactinemic states in which 85 percent of the serum prolactin elutes in a 22,000-dalton peak. Hence, macroprolactinemia is apparently a nonprogressive condition and a novel cause of massive hyperprolactinemia.

Adult↗

PubMed1985

The natural history of idiopathic hyperprolactinemia.

Idiopathic hyperprolactinemia (IH) can be defined as the presence of elevated serum PRL levels in a patient in the absence of demonstrable pituitary or central nervous system disease and of any other recognized cause of increased PRL secretion. This study examined the long term clinical outcome of 41 patients (mean age, 26 yr) with IH followed for up to 11 yr (mean, 5.5 yr). Initial and final PRL levels were determined by RIA in the same laboratory. A correction factor was used to obviate periodic changes in the potency of the NIH standards used in the PRL assay, so that all results are expressed in terms of the original VLS no. 1 standard. The initial serum PRL levels ranged from 27.2-243 ng/ml, with a mean of 57 ng/ml. Only three patients had initial serum PRL levels greater than 100 ng/ml. All had a normal skull x-ray and/or brain computed tomographic scan during their initial visit. All 41 patients had galactorrhea and/or amenorrhea. Serum PRL levels remained the same, decreased, or returned to normal in 34 of 41 patients. The mean PRL level at the time of reevaluation was 35 ng/ml. Thirty-four percent of the patients had a normal serum PRL level. Only 17% of the patients had serum PRL levels that were significantly higher (greater than 50% of their original value). Six of 9 patients with an initial serum PRL level less than 40 ng/ml had normal levels. One patient developed a pituitary tumor (initial PRL, 150 ng/ml). All patients reevaluated with brain computed tomographic scans had normal pituitary size. No patient reported a worsening of signs or symptoms, and in many, improvement (n = 16) or complete resolution (n = 8) of the amenorrhea and/or galactorrhea occurred. Twenty-seven spontaneous or bromocriptine-induced normal pregnancies and deliveries occurred without development of a pituitary tumor. Therefore, our data clearly challenge the use of ablative pituitary therapy for IH and raises questions of the benefit of chronic medical therapy for this condition.

Adult↗

PubMed1985

Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses.

This study reports the presence of a large molecular sized PRL as the major form of circulating immunoactive PRL in five women with idiopathic hyperprolactinemia and normal menses. Gel filtration patterns of serum from these patients revealed 98-100% predominance of a 150,000- to 160,000-dalton PRL in contrast to the predominance of the 22,000-dalton species in other hyperprolactinemic patients. This 150,000- to 160,000-dalton PRL was immunologically similar to the 22,000-dalton PRL, and its size on gel filtration was not altered using denaturing conditions. With reduction of disulfide bonds, there was a shift of the peak I PRL to smaller mol wt peptides. In addition, studies of one woman with idiopathic hyperprolactinemia and normal menses revealed preservation of 98% peak I predominance during physiological and pharmacological perturbations of PRL secretion. Finally, assay of the bioactivity of the large molecular sized PRL in the Nb2 rat lymphoma line revealed diminished activity compared to the 22,000-dalton species. This latter finding may help explain the maintenance of normal menses and relative lack of clinical signs in patients with this form of hyperprolactinemia.

Adenoma↗

PubMed1985

Serum carotene levels in female long-distance runners.

Hypercarotenemia has been associated with anorexia nervosa and hypothalamic amenorrhea. With the emergence of a spectrum of menstrual dysfunction, including anovulation in women runners, the hypothesis of hypothalamic amenorrhea in these patients has been formulated. Other authors have proposed exercise-associated amenorrhea to be distinct from hypothalamic amenorrhea based on endocrine profiles. Using carotene as an index test of hypothalamic amenorrhea, we have studied female long-distance runners (greater than 25 miles/week) and have found no difference in the carotene levels between ovulatory (midfollicular) and anovulatory runners. These data support other evidence that exercise-associated amenorrhea is distinct from hypothalamic amenorrhea.

Adult↗

PubMed1984

The diurnal variations of serum prolactin levels before and during pregnancy in normal and hyperprolactinemic patients.

The pattern of 24-hour secretion of prolactin was evaluated in three normal pregnant subjects at the tenth, twenty-fourth, and thirty-sixth gestational week. A similar study was performed in three hyperprolactinemic subjects throughout the course of their gestations. The findings confirm the progressive rise in serum concentrations of prolactin throughout pregnancy in normal subjects, with a tendency to blunting of the ratio of the nighttime mean to the daytime mean ( meanss / meansa ) as pregnancy progresses. One hyperprolactinemic subject (nontumoral) followed this pattern but demonstrated blunting initially and throughout pregnancy. The other two hyperprolactinemic subjects (one tumoral and one nontumoral) demonstrated an unexpected response in that they remained unresponsive to the increasing concentrations of estradiol throughout pregnancy.

Adult↗

PubMed1984

Assessment of mammary lactogenic receptor changes in pregnant rabbits.

Lactogenic receptor was purified from rabbit mammary tissue and used to generate an antiserum in goats. The purified lactogenic receptor material bound lactogenic hormones specifically and reversibly. Antiserum generated in a goat bound a labeled human growth hormone/receptor complex; this was displaced by nonlabeled solubilized receptor preparations. This was used as a radioimmunoassay and was able to detect 0.037 fmol of lactogenic receptor. The specificity of the radioimmunoassay for lactogenic receptor was supported by three lines of evidence; first, the ligand used in the radioimmunoassay was an iodine 125-labeled human growth hormone/receptor combination; therefore, only membrane protein with structural homology to the protein which bound 125I-labeled human growth hormone competed for binding to the antiserum; second, depletion of radioreceptor binding sites by affinity chromatography with ovine prolactin as the fixed ligand was detected; third, an increase in breast lactogenic receptor during pregnancy was detected by both radioreceptor assay and the radioimmunoassay. We found a progressive increase in lactogenic receptors by radioimmunoassay which corresponded to parallel increases by radioreceptor assay in rabbit mammary tissue during pregnancy.

Animals↗

PubMed1984

Pentagastrin promotes prolactin release in patients with medullary carcinoma of the thyroid.

Both calcitonin and gastrin have been found in the mammalian central nervous system, including the pituitary. Following a pentagastrin infusion in several patients with medullary carcinoma of the thyroid, we noted a coincident increase in plasma calcitonin and prolactin (PRL) levels. In order to evaluate further the influence of pentagastrin on human PRL release, a pentagastrin infusion was administered to 13 patients with active medullary carcinoma of the thyroid (MTC), eight subjects with inactive MTC, eight family members without MTC, and ten normal subjects. Plasma mean +/- SE PRL levels were significantly (P less than 0.01) increased in the active MTC patients from 7.6 +/- 0.5 to 12 +/- 1.4 ng/mL by 15 minutes post pentagastrin. Plasma mean +/- SE calcitonin levels increased in parallel with the plasma PRL levels from 0.28 +/- 0.1 to a peak of 1.9 +/- 0.9 ng/mL at 5 minutes post pentagastrin. A significant (P less than 0.05) correlation was found between the percentage increase in plasma calcitonin concentrations and plasma PRL levels at five and ten minutes post pentagastrin stimulation in this group of active MTC patients. Significant increases in serum calcitonin levels in the other groups post pentagastrin were of lesser magnitude and were not associated with a significant increase in PRL release. This latter observation suggested that neither the stress of the infusion nor the multiple endocrine neoplasia type 2 nor the pentagastrin was responsible for the observed increase in plasma PRL levels in the active MTC patients. These findings suggest, but do not prove, that calcitonin is a PRL-releasing factor in humans.

Calcitonin↗

PubMed1984

Pregnancy complicated by insulinoma.

Gestational hypoglycemia may result from either reactive hypoglycemia or complications related to the pregnancy. We report a 19-year-old pregnant patient with insulinoma who was treated successfully by distal pancreatectomy during the first trimester. A high index of suspicion was required for the diagnosis since abnormal immunoreactive insulin (IRI) and glucose (G) ratios (I/G) greater than 0.3 can be found in non-insulinoma normal pregnancy. The incidence of insulinoma complicating pregnancy is unknown, but it is important since gestational hypoglycemia can be associated with an increased perinatal mortality and morbidity similar to that of gestational hyperglycemia.

Abortion, Induced↗

PubMed1984

Twenty four-hour prolactin profiles and prolactin responses to dopamine in long distance running women.

Long distance women runners have a high incidence of oligoamenorrhea. In order to study the possible role of PRL in contributing to their menstrual dysfunction, we evaluated PRL secretion in eumenorrheic (n = 7) and oligomenorrheic runners (n = 9) who averaged 25-50 miles/week, as well as nonrunning women (n = 5) during the midfollicular phase of their cycles. Serum estradiol, progesterone, testosterone, FSH, LH, TSH, and T4 were similar among the three groups. The mean 24-h +/- SE PRL concentrations between the three groups: nonrunners, 12.9 +/- 0.6 ng/ml; eumenorrheic runners, 13.5 +/- 0.4 ng/ml; and oligomenorrheic runners, 15.0 +/- 0.8 ng/ml, were not significantly different. A dopamine (DA) infusion, 0.004 micrograms/kg X min, produced physiologic serum DA levels in these subjects. The nadir of serum PRL levels during DA infusion was similar in each group, which argues against an abnormality in dopaminergic tone in the runners with menstrual dysfunction. Our findings of normal 24-h PRL secretion and appropriate PRL responses to DA in women runners with menstrual dysfunction do not support a role for PRL in this disorder.

Adolescent↗

PubMed1983

Physiological concentrations of prolactin can promote the growth of human breast tumor cells in culture.

There is only indirect evidence at present to suggest a role for PRL in either the genesis or progression of human breast cancer. Here, we report the results of experiments in primary cultures of breast tumor cells from a hyperprolactinemic breast cancer patient who had an elevated mean 24-h PRL concentration but a normal diurnal variation of PRL release. The effects of PRL and GH on the growth of the dispersed cells from the breast tumor was evaluated in monolayer culture using a recently developed microculture technique. Pharmacological quantities of GH produced significant increases in the number of population doublings of the breast tumor cells. Also, PRL concentrations present in the patient's circulation were demonstrated to significantly increase the number of population doublings of the breast tumor cells obtained in primary cultures. Thus, physiological concentrations of PRL stimulated the growth of breast tumor cells from this premenopausal patient.

Adult↗