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Biomedical subjects

R Rolland

Publications and source records attributed to R Rolland.

16 recordsLinked to original sources

Inhibition of puerperal lactation by bromocriptine.

Puerperal lactation is regulated by a complex of hormones, including in particular prolactin. In a few instances prevention of lactation is desirable on medical grounds. However, most Western-European women who do not nurse their babies choose not to do so for personal reasons. In two double-blind studies the effect of bromocriptine was compared with that of placebo and an oestrogen/androgen compound. Bromocriptine prevented both milk secretion and engorgement of the breasts very effectively. It is clearly a better and more specific inhibitor of lactation than the combined oestrogen/androgen compound. Its effect is through the blockade of pituitary prolactin release. As normoprolactinaemia is reached, normal ovarian function is restored in bromocriptine treated women. To prevent the occurrence of a rebound lactation phenomenon, the drug has to be administered continuously for at least a fortnight.

Bromocriptine

Hyperprolactinemia and hypogonadism in the human female.

Prolactin is a mammotropic hormone essential for the initiation of lactation. It also influences ovarian function; during hyperprolactinemia hypogonadism occurs. This is true for pathological forms of hyperprolactinemia but also for the early puerperium when there is physiological hyperprolactinemia. Amenorrhea is a better parameter of hyperprolactinemia than galactorrhea. The mechanisms by which prolactin disrupts ovarian function are not as yet fully understood; it probably alters hypothalamic neurotransmitter content through a direct feedback mechanism resulting in a decrease of Gn-RH. However, the direct effect of prolactin-producing pituitary tumors on the capacity of the gonadotrophs or a direct interference of prolactin at the gonadal level are also possibilities. Hyperprolactinemia can be treated very effectively with bromocriptine and this drug appears to have become the favorite form of treatment. In the case of obvious tumors hypophysectomy is indicated. When there are smaller tumors irradiation of the pituitary gland previous to bromocriptine treatment may prevent expansion of the gland during subsequent pregnancy.

Amenorrhea

Visual abnormalities in a pregnancy following bromocriptin medication.

A patient with hyperprolactinemia, amenorrhea, and an enlarged sella turcica, but without galactorrhea, was treated with Bromocriptin to effect restoration of ovarian function. The subsequent pregnancy was without problems from an obstetric point of view, but visual field abnormalities developed progressively, leading to termination of the pregnancy in the 39th week. However, within 1 week after delivery, the field defects disappeared and the visual acuity returned to normal.

Adult

Demonstration of specific binding of prolactin by porcine corpora lutea.

Subcellular fractions from porcine corpora lutea of the reproductive cycle and pregnancy were shown to have specific binding sites for ovine prolactin (oPRL). Aside from oPRL, only ovine and bovine growth hormone preparations competed with [125I]iodo-oPRL for its binding site. These cross reactions were at a level consistent with the prolactin contamination of these preparations. Rat growth hormone, FSH, LH, TSH, insulin, and ACTH exhibited negligible cross-reactivity. Both corpora hemorrhagica and albicantia had lower specific binding of [125I]iodoPRL than did active corpora lutea of the reproductive cycle, while corpora lutea of pregnancy demonstrated a nearly 5-fold increase in specific binding compared with that of the cycle. Corpora lutea from animals with larger fetuses (greater gestational age) bound the most prolactin. Analysis of data from cold competition studies employing weighted non-linear least-square fitting to a three-parameter model, showed high-affinity binding of oPRL with an association constant (Ka, 23 C) of 2.0 X 10(9)M-1 for the binding site of the corpus luteum of the cycle. The Ka shows no appreciable change with pregnancy. In contrast, the binding site concentration (N) increases markedly from less than 10 fmol/mg protein in corpora lutea from non-pregnant animals to approximately 40 fmol/mg protein for animals at a gestational stage of 40-46 days. The observed Ka's are similar to values obtained for the prolactin binding site in porcine granulosa cells harvested from unruptured follicles and to the prolactin-binding site in the mammary gland.

Animals

The role of prolactin in the restoration of ovarian function during the early post-partum period in the human female. I. A study during physiological lactation.

Serial plasma levels of prolactin, follicle-stimulating/ml hormone (FSH), luteinizing hormone (LH), 17beta-oestradiol (E) and progesterone (P) were determined by radio-immunoassay in ten healthy women during late pregnancy and puerperium until the occurrence of the first menstruation, at which moment an endometrial biopsy was taken. Prolactin concentrations, which were high during late pregnancy and the early post-partum period, declined thereafter but remained above 30 ng

Cell Division

The role of prolactin in the restoration of ovarian function during the early post-partum period in the human female. II. A study during inhibition of lactation by bromergocryptine.

Serial plasma levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17beta-oestradiol (E) and progesterone (P) were determined by radioimmunoassay in ten healthy women during late pregnancy and the puerperium during inhibition of lactation by Bromergocryptine. This medication was continued until the occurrence of the first menstruation, at which point an endometrial biopsy was taken. Prolactin was very effectively suppressed by Bromergocryptine in all patients, as was lactation. FSH was nearly undetectable during late pregnancy and the first week post-partum with an increase back to normal levels between day 7 and 12. Thereafter FSH levels were within the normal cyclic range. Following clearance of human chorionic gonadotrophin (HCG) during the first 2 weeks post-partum, LH was found within the normal cyclic range in all patients. From day 7 E increased in nine of ten patients to reach levels during the fourth week which are seen normally at the moment of the pre-ovulatory E-surge in cycling women. In eight of the ten cases this was concomitant with high levels of LH. The tenth patient showed a high E level at day 36. P was fully excreted within 7 days and remained low until approximately day 20. Thereafter an increase was demonstrated with levels as found during the luteal stage of the menstrual cycle in nine patients within 33 days and within 40 days in all ten patients. The endometrial biopsies showed clear signs of secretory activity. The probable action of prolactin on ovarian function is discussed. It is suggested that during the puerperium the ovaries are the more refractory part of the hypothalamicpituitaryōvarian axis, due probably to an influence of prolactin on the ovarian steroid synthesis.

Bromine

Demonstration of a specific receptor for prolactin in porcine granulosa cells.

Porcine granulosa cells and subcellular fractions from these cells have been shown to have a specific receptor for ovine prolactin (OPRL). Ovine growth hormone demonstrated 7% of the potency of OPRL in displacing 125I-OPRL from its binding site; FSH, TSH, LH, insulin and ACTH showed negligible cross-reactivity. Scatchard analysis of the displacement curves suggested that 125I-OPRL has a high affinity for its receptor with a dissociation constant (Kd) for the granulosa cell-receptor of 7.4-7.7 times 10(-10) M with no change as the follicle enlarges. In contrast, the specific binding of prolactin decreased markedly with maturation of the follicles with an apparent decrease in binding sites/cell from 555 in small follicles to 300 in large (preovulatory) follicles. The demonstrated Kd's were within the range of prolactin concentrations easily attained in vivo and were in good agreement with values obtained in our laboratory and elsewhere for the prolactin receptor from mammary gland and other tissues. Consequently, these studies may provide a basis for a better understanding of the role of prolactin in ovarian function.

Animals