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D L Kleinberg

Publications and source records attributed to D L Kleinberg.

51 records · Page 3Linked to original sources
PubMed1979

Evidence that prolactin stimulates alpha-lactalbumin production in mannary tissues from premenarcheal rhesus monkeys.

PRL was found to stimulate marked increases in alpha-lactalbumin production in six of eight specimens of mammary tissue from premenarcheal rhesus monkeys, and a lesser increase was seen in a seventh. Even without added PRL, low concentrations of this milk protein (mean total alpha-lactalbumin production, 1.9 ng/dish) were released into the organ culture medium bathing these relatively immature tissues; most of the epithelial elements were ductal. Under similar conditions, significantly higher concentrations of alpha-lactalbumin (mean total production, 23.4 ng/dish) were released from tissues of sexually mature animals in which lobulo-alveolar elements were abundantly present in addition to ducts. When tissues from premenarcheal animals were exposed to ovine PRL, alpha-lactalbumin concentration in medium and tissue homogenates were increased significantly. Overall, mean total alpha-lactalbumin production rose to 12.9 (P less than 0.02) and 40.5 (P less than 0.02) ng/dish in response to 100 and 1000 ng/ml ovine PRL, respectively. In those cases in which both medium and tissue homogenates were analyzed, increases were parallel. These findings indicate that PRL has a lactogenic effect on mammary tissue from sexually immature and mature rhesus monkeys.

Animals↗
PubMed1978

Prolactin stimulation of alpha-lactalbumin in normal primate mammary gland.

An in vitro system has been developed to examine the effects of PRL on the normal primate mammary gland. alpha-Lactalbumin a milk protein, was found in breast tissue samples from 17 of 19 primates representing several Macaca and Papio species; concentrations ranged from 10-768 ng/mg protein. That none of the animals was pregnant or lactating and half were nulliparous indicates that milk protein production takes place under normal circumstances, even in breast tissue of nonlactating animals. Studies of the effect of PRL on alpha-lactalbumin production in these tissues in organ culture revealed that PRL maintained existing or stimulated new production of alpha-lactalbumin for periods of up to 9 days. Measurement of alpha-lactalbumin in medium bathing mammary tissue from three animals revealed that mean alpha-lactalbumin production during days 7-9 when PRL was added (100 and 1000 ng/ml) was 11 and 59 times greater, respectively, than control. Simultaneous measurement of tissue concentrations of alpha-lactalbumin revealed that those tissues maintained with PRL (1000 ng/ml) had a mean concentration of alpha-lactalbumin that was 61 times that of controls without PRL. PRL consistently maintained or increased alpha-lactalbumin production in tissues from all 22 primates tested. Even in those premenarchal animals in whose mammary tissue alpha-lactalbumin was undetectable initially, PRL stimulated alpha-lactalbumin production in a dose-related fashion. In contrast, when PRL was absent from medium, alpha-lactalbumin concentrations decreased at 9 days to less than 20% of the initial 3-day value in all cases. These studies provide evidence that mammary tissue from normal nonlactating, nonpregnant primates produces milk proteins and that when tissues are exposed to PRL in culture, production of alpha-lactalbumin is stimulated.

Animals↗
PubMed1978

The pathophysiology of hyperprolactinemic states and the role of newer ergot compounds in their treatment.

Studies of prolactin secretion in humans have confirmed the concept, derived originally from animal investigations, that prolactin is predominantly controlled by tonic inhibition from the hypothalamus. The locus of action of dopamine and dopaminergic agents such as the ergot alkaloids inhibiting prolactin secretion appears to be primarily at the pituitary level, though a hypothalamic action to increase secretion of prolactin inhibitory factor may also contribute. Prolactin hypersecretion, through any of several possible mechanisms, is frequently but not always found in patients with galactorrhea. Recent studies have shown that hyperprolactinemia is considerably more common than was previously appreciated among patients without galactorrhea. It is present in at least two-thirds of all patients with pituitary tumors and in a significant minority of patients with secondary amenorrhea. Its clinical measurement in these conditions is therefore of considerable diagnostic importance. Whatever the pathophysiology of its production, hyperprolactinemia of all forms is responsive to treatment with the newer ergot alkaloids. The potential use of these agents for therapeutic purposes, particularly in the treatment of infertility, appears to be wider than was originally anticipated.

Acetonitriles↗
PubMed1977

Galactorrhea: a study of 235 cases, including 48 with pituitary tumors.

An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea, and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or pituitary tumor, stopped galactorrhea in over 50 per cent, restored menses in over 70 per cent, and allowed pregnancy in three.

Acromegaly↗
PubMed1977

Positive feedback of oestrogen on LH secretion in women in neuroleptic drugs.

The effect of a-adrenergic and dopaminergic blockade on the ability of pituitary-hypothalamic axis to produce an LH surge in response to oestrogen, was studied in eleven women treated with the neuroleptic agents haloperidol, fluphenazine or chlorpromazine. Seven women on no medication were controls. 6.6 mg of oestradiol benzoate (OB) was injected i.m. after control serum was obtained and daily serum samples were obtained for four additional days. Sera were assayed for total oestrogens, LH, FSH and prolactin. Six of seven women in the control group and eight of eleven women treated with neuroleptic agents had LH surges to OB challenge. The mean prolactin of the treated women was 33.1 +/- 3.6(SEM) ng/ml and the mean prolactin of the controls was 14.9 +/- 1.5(SEM) ng/ml, P less than 0.005). Elevated levels of circulating prolactin did not prevent an LH surge to OB challenge. These results indicate that even in subjects with catecholamine blockade, an LH surge can be induced. This contrasts to results obtained in rats and suggests that the control mechanism of LH surge production differs in rodents and humans.

Adolescent↗
PubMed1977

Studies on human alpha-lactalbumin: radioimmunoassay measurements in normal human breast and breast cancer.

A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a milk protein, has been developed in order to examine the effect of prolactin on the human breast in normal and diseased states. Samples of milk from nursing mothers and from men and women with galactorrhea were found to contain milligram concentrations of this protein. In serum, 8 of 25 normal men and 18 of 44 normal women had detectable concentrations of alpha-lactalbumin. Significantly higher levels of alpha-lactalbumin were found in 17 of 19 women during pregnancy who were not actively lactating. All nursing mothers were found to have distinctly elevated serum alpha-lactalbumin concentrations. In a group of 17 female patients with phenothiazine induced prolactin elevations (mean 29.4 ng/ml), the mean serum alpha-lactalbumin of 17.3 ng/ml was significantly higher than in normal female volunteers. Patients with gynecomastia were not noted to have elevated alpha-lactalbumin. In vitro, homogenates of normal breast and carcinoma tissue from the same individuals revealed that in 9 of 17 patients alpha-lactalbumin was present in higher concentrations in normal than in cancerous tissue. Overall, alpha-lactalbumin was found in 48.5% of homogenates and 41% of organ cultures of normal breast tissue from cancer patients. In contrast, it was present in only 19% of homogenates and 21% of cultures of carcinoma tissue, indicating that the cancer tissue may lose its ability to produce alpha-lactalbumin. Differences in biologic behavior were found in some tumors. In 2 cases homogenates of breast cancer tissue had much higher concentrations of alpha-lactalbumin than the normal tissue, and in 3 of 33 tumors studied in organ culture prolactin increased alpha-lactalbumin output.

Adolescent↗
PubMed1975

Human alpha-lactalbumin: measurement in serum and in breast cancer organ cultures by radioimmunoassay.

A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a major milk protein, is described. Some normal men and women have detectable levels of alpha-lactalbumin in their blood. High values are found in nursing mothers and many patients with galactorrhea. Alpha-Lactalbumin is found in some breast cancer organ cultures. In addition, alpha-lactalbumin output was stimulated by ovine prolactin in 2 of the 19 tumors studied.

Adolescent↗
PubMed1971

Human prolactin: measurement in plasma by in vitro bioassay.

Prolactin has been measured in unextracted human plasma by a sensitive and specific in vitro bioassay. Secretory activity of breast tissue fragments from mid-pregnant mice, incubated in organ culture with human plasma, serves as the histologic end point. Sensitivity is 5 ng/ml (0.14 mU/ml) or somewhat better for ovine prolactin, and approximately 0.42 mU/ml for prolactin activity of human plasma at the dilutions used in the assay. Human growth hormone as it circulates in blood, like the material extracted from pituitary glands, is strongly lactogenic. Antisera to human growth hormone are capable of completely neutralizing the prolactin effect of large amounts (600 ng/ml) of human growth hormone added to the system. Plasma prolactin activity is less than 0.42 mU/ml in normal men and women. Of 26 patients with nonpuerperal galactorrhea, 14 had elevated prolactin activities ranging from 0.42 to 3.5 mU/ml. Growth hormone levels by radioimmunoassay were far too low, in general, to account for the observed prolactin activity. All of 14 nursing mothers, 1-30 days post partum, had elevated prolactin activity with a mean of 2.29 and a total range of 0.56-4.5 mU/ml. Growth hormone was in the low normal range in all of these subjects. Seven patients on psychoactive drugs of the phenothiazine series similarly had elevated prolactin activity with low growth hormone. Antiserum to human growth hormone, when preincubated with plasma samples from each of these three groups of subjects, produced no significant inhibition of prolactin activity. In two acromegalic patients with markedly elevated growth hormone levels, antiserum to growth hormone produced complete inhibition of prolactin activity in one and partial inhibition in the other. These studies indicate that human growth hormone and human prolactin are separate molecules, with little if any immunologic cross-reactivity, at least as demonstrated by the antisera used in this study, and that their release is governed by different physiologic mechanisms.

Acromegaly↗
PubMed1970

Prolactin: evidence that it is separate from growth hormone in human blood.

A highly sensitive bioassay has been developed for prolactin, which uses a mammalian end organ and which is capable of measuring the hormone in unextracted human plasma. High prolactin activity, largely neutralizable with antiserum to human growth hormone, is stimulated along with high immunoassayable growth hormone by insulin-induced hypoglycemia. High prolactin activity, not neutralizable with antiserum to growth hormone, exists with low concentrations of plasma growth hormone in postpartum patients and patients with galactorrhea.

Acromegaly↗