Subset-specific effects of sex hormones and pituitary gonadotropins on human lymphocyte proliferation in vitro. 1993

B H Athreya, and J Pletcher, and F Zulian, and D B Weiner, and W V Williams
Children's Seashore House, Philadelphia, Pennsylvania.

Clinical observations on patients with systemic lupus erythematosus and rheumatoid arthritis and studies in murine models of autoimmune diseases suggest an important role for the sex and pituitary hormones in immune function. Estrogen and testosterone have been shown to modulate B cell functions in vitro. Prolactin (PRL) has been shown to have immunomodulatory functions. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) have homology to thioredoxin, a potentiator of T-cell growth. We therefore studied the proliferative response of peripheral blood mononuclear cells (PBMC) from normal adult males to various stimuli in the presence or absence of estradiol (E2), testosterone (Te), PRL, FSH, and LH and the effect of these hormones on T-cell subsets by flow cytometry. Unfractionated PBMC were stimulated with 1% phytohemagglutinin (PHA) (polyclonal activation), anti-CD3 (T-cell receptor stimulation), or recombinant interleukin 2 (IL-2) (late stages of activation). We assessed the effects of E2 (0.3-30 ng/ml), Te (3-300 ng/ml), PRL (2-200 ng/ml), FSH (1-100 mIU/ml), and LH (1-100 mIU/ml). E2 and Te had no consistent effect on PBMC proliferation in response to any of the stimuli. E2 significantly decreased the percentage of CD4+ cells following PHA stimulation (P = 0.022), while significantly enhancing the percentage of CD8+ cells following IL-2 stimulation (P = 0.007). Te significantly increased the percentage of CD4+ cells following IL-2 stimulation (P = 0.03). PRL enhanced proliferation in response to IL-2 and PHA without subset-specific effects. FSH and LH both enhanced IL-2-induced proliferation, particularly in physiological doses (10 mIU/ml). FSH at 100 mIU/ml significantly decreased the percentage of CD4+ cells in unstimulated cultures (P = 0.003), while it enhanced the percentage of CD8+ cells following PHA stimulation (P = 0.004). The enhancement in CD8+ cells appeared the most marked in the CD8+CD28+ subset. LH at 10 mIU/ml significantly enhanced the percentage of CD4+ cells following IL-2 stimulation (P = 0.009) and at higher doses (100 mIU/ml) enhanced the percentage of CD4+ cells following PHA stimulation (P = 0.011). Thus, sex steroids and adenohypophyseal hormones (PRL, FSH, and LH) have subset-specific effects on T-cell activation which may influence sex-related differences in immune response.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D007986 Luteinizing Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity. ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008297 Male Males
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
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D004967 Estrogens Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Estrogen,Estrogen Effect,Estrogen Effects,Estrogen Receptor Agonists,Estrogenic Agents,Estrogenic Compounds,Estrogenic Effect,Estrogenic Effects,Agents, Estrogenic,Agonists, Estrogen Receptor,Compounds, Estrogenic,Effects, Estrogen,Effects, Estrogenic,Receptor Agonists, Estrogen
D005260 Female Females
D005640 Follicle Stimulating Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D006065 Gonadotropins, Pituitary Hormones secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR) that stimulate gonadal functions in both males and females. They include FOLLICLE STIMULATING HORMONE that stimulates germ cell maturation (OOGENESIS; SPERMATOGENESIS), and LUTEINIZING HORMONE that stimulates the production of sex steroids (ESTROGENS; PROGESTERONE; ANDROGENS). Pituitary Gonadotropins

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