Biomaterial Database

Prolactin release-inhibitory effects of progesterone, megestrol acetate, and mifepristone (RU 38486) by cultured rat pituitary tumor cells. 1987

S W Lamberts, and P van Koetsveld, and T Verleun

The prolactin (PRL) release-inhibitory effects of progesterone, dexamethasone, megestrol acetate, and mifepristone (RU 38486) were studied in cultured pituitary tumor cells prepared from the 7315a and 7315b tumor. Both tumors contain similar numbers of estrogen and progesterone receptors, while only the 7315a tumor also has glucocorticoid receptors. PRL release by the 7315a tumor was stimulated by low concentrations of dexamethasone (10(-10)-10(-9) M) and was inhibited in a dose-dependent manner by higher concentrations (-86% by 10(-7) M). In contrast only 10(-6) and 10(-5) M dexamethasone inhibited PRL release by the 7315b cells by 14 and 24%, respectively. Progesterone caused a dose-dependent inhibition of PRL release, which was similar in the 7315a and b tumor cells. Progesterone (10(-9) M) inhibited PRL release by 62% and this inhibition was completely prevented by 100 nM estradiol, which was stimulatory by itself (+48%). Mifepristone inhibited PRL release by both tumors in a dose-dependent manner, but more powerfully in the 7315a tumor; 10(-6) M concentrations of the compound inhibited PRL release by 52% in the 7315a and by 26% in the 7315b tumor cells. Megestrol acetate inhibited PRL release in both tumors in a dose-dependent manner, but more powerfully in the 7315b tumor; a 10(-8) M concentration of the compound inhibited PRL release by 54% in the 7315b tumor and by 14% in the 7315a tumor. In the 7315a tumor 10(-9) M megestrol acetate even stimulated PRL release, suggesting a dexamethasone-like glucocorticoid effect of the drug on this tumor. Thereafter the interaction of mifepristone and megestrol acetate on PRL release was investigated. In the 7315a tumor cells different combinations of both drugs neutralized each other's inhibitory effects on PRL release, while both drugs had additional inhibitory effects on PRL release by 7315b tumor cells. Changes in PRL release by the cultured pituitary tumor cells were in all instances closely correlated with changes in the PRL content, the protein content, and the DNA content of the tumor cells. This suggests that the inhibitory effect of the compounds studied on PRL release is paralleled by an inhibitory effect on the number of pituitary tumor cells. These studies show the importance of the presence of glucocorticoid receptors in the effectiveness and mechanism of action of the antitumor effects of megestrol acetate and mifepristone.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D008535	Megestrol	A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer.	17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione,Pregna-4,6-diene-3,20-dione, 17-hydroxy-6-methyl-
D010911	Pituitary Neoplasms	Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.	Pituitary Cancer,Cancer of Pituitary,Cancer of the Pituitary,Pituitary Adenoma,Pituitary Carcinoma,Pituitary Tumors,Adenoma, Pituitary,Adenomas, Pituitary,Cancer, Pituitary,Cancers, Pituitary,Carcinoma, Pituitary,Carcinomas, Pituitary,Neoplasm, Pituitary,Neoplasms, Pituitary,Pituitary Adenomas,Pituitary Cancers,Pituitary Carcinomas,Pituitary Neoplasm,Pituitary Tumor,Tumor, Pituitary,Tumors, Pituitary
D011374	Progesterone	The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.	Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D011388	Prolactin	A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.	Lactogenic Hormone, Pituitary,Mammotropic Hormone, Pituitary,Mammotropin,PRL (Prolactin),Hormone, Pituitary Lactogenic,Hormone, Pituitary Mammotropic,Pituitary Lactogenic Hormone,Pituitary Mammotropic Hormone
D011915	Rats, Inbred BUF	An inbred strain of rat that is used for cancer research, particularly the study of CARCINOGENESIS	Rats, Inbred Buffalo,Rats, BUF,BUF Rat,BUF Rat, Inbred,BUF Rats,BUF Rats, Inbred,Buffalo Rats, Inbred,Inbred BUF Rat,Inbred BUF Rats,Inbred Buffalo Rats,Rat, BUF,Rat, Inbred BUF
D011960	Receptors, Estrogen	Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.	Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D011965	Receptors, Glucocorticoid	Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.	Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D011980	Receptors, Progesterone	Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.	Progesterone Receptors,Progestin Receptor,Progestin Receptors,Receptor, Progesterone,Receptors, Progestin,Progesterone Receptor,Receptor, Progestin
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.