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Biomedical subjects

W H Utian

Publications and source records attributed to W H Utian.

At least 19 recordsLinked to original sources
PubMed1991

Sex steroids and growth factors differentially regulate the growth and differentiation of cultured human endometrial stromal cells.

We have studied the interaction between growth factors and sex steroids in regulating human endometrial stromal cell growth and differentiation using an in vitro serum-free cell culture model system. None of the growth factors [epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin, insulin-like growth factor-I (IGF-I), IGF-II, or platelet-derived growth factor] stimulated the growth of human endometrial stromal cells grown in progestin-free medium. However, the growth of progestin-treated cultures was dramatically increased by EGF, bFGF, or platelet-derived growth factor, but not by insulin, IGF-I, or IGF-II. Estrogen could not substitute for progesterone in this protocol, and coadministration of estrogen with progestin did not enhance the response over that to progesterone alone. In contrast to their positive effects on growth, only EGF, not bFGF, stimulated stromal cell differentiation, as measured by an increase in PRL, laminin, and fibronectin production; moreover, stimulation of differentiation was dependent upon the presence of progestin in the culture medium. Thus, human endometrial stromal cell growth is 1) regulated by a discrete set of growth factors, only a subset of which regulates stromal cell differentiation; and 2) regulation of stromal cell growth and stromal cell differentiation by growth factors is progestin dependent. Our results provide direct evidence for interaction between growth factors and sex steroids in the regulation of stromal cell growth and differentiation in vitro and suggest that growth factors may be absolutely required in conjunction with progesterone for the decidual response in vivo.

Cell Differentiation↗
PubMed1990

Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues.

The human uterus repeatedly exhibits cyclic biochemical and cytological changes during the reproductive period of life. These changes are the result of a well-characterized endocrine network involving the hypothalamus, pituitary, and ovary. The exact nature of the mechanism(s) by which the sex steroids act on the uterus remains to be elucidated. Possible local mediators of hormonal action on the uterus include polypeptide growth factors. Using the method of RNA transfer blot hybridization, we have analyzed tissue samples from the cycling human endometrium and tissue samples of human myometrium and myometrial benign tumor (leiomyoma) for the presence of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) RNA. All the uterine tissues examined possessed RNA for PDGF-B chain and IGF-I and -II. Two transcripts were observed for PDGF-B chain, four were observed for IGF-I, and eight were observed for IGF-II. Overall, the relative abundance of PDGF-B chain RNA was consistent in all of the uterine tissues examined. In contrast, IGF RNA relative abundance varied. IGF-I RNA was highest in late proliferative stage endometrium, and IGF-II RNA was highest in early proliferative stage endometrium. Both IGF-I and IGF-II RNAs were greater in amount of leiomyoma than in myometrium. The increased IGF-I RNA in late proliferative-stage human endometrium correlates with the known elevation of estradiol secretion by the ovary and the increased concentration of uterine estradiol receptors during this stage of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrium↗
PubMed1990

The menopause in perspective. From potions to patches.

This article attempts to survey our current understanding of the human female climacteric and the role of hormone replacement in its treatment. As a potential endocrinopathy, the climacteric deserves appropriate diagnostic recognition and selective preventive pharmacotherapy. The impact of sometimes conflicting influences such as nutritional, dietary or lifestyle changes, exercise, smoking, drugs, alcohol and other medications, all need differentiation from true hormonal responses. The climacteric, one syndrome occurring over a period of time, has potentially lethal effects, notably coronary heart disease and complications of osteoporotic fractures. However, therapy itself carries major problems, the cancer question being the most important. The dilemma of risk-benefit planning is reviewed and likely future developments are outlined. The role of the new North American Menopause Society is explained.

Endocrine System Diseases↗
PubMed1990

Maintenance of in vivo-like keratin expression, sex steroid responsiveness, and estrogen receptor expression in cultured human ectocervical epithelial cells.

In the present manuscript we demonstrate that ectocervical epithelial cells (ECE cells) retain a high degree of differentiated function when cultured using feeder layers. We characterize the cultured cells with respect to morphology, expression of cytokeratins, responsiveness to sex steroids, and the presence of estrogen-binding sites. Like ectocervical cells in vivo, the cultured cells display a typical epithelial cell morphology and undergo extensive stratification and envelope (superficial cell) formation. Like the in vivo ectocervical epithelium, the cultured ECE cells express type I cytokeratins K13, K14, K16, K17, and K19 and type II cytokeratins K5 and K6. Under normal culture conditions, however, cytokeratins K1, K2, K4, K11, and K15, which are expressed in vivo, are not expressed. An interesting finding is that ECE cells, in contrast to endocervix and epidermis in vivo and cultured epidermal keratinocytes, express very abundant levels of K13. In fact, K13 appears to be a specific marker of ECE cells in the female reproductive tract. When incubated with 10 nM diethylstilbestrol, ECE cell envelope production increased 3-fold, while incubation with 100 nM progesterone decreased envelope formation 3.4-fold. Simultaneous incubation with progesterone antagonized the diethylstilbestrol stimulation. Thus, in vivo-like sex steroid regulation of ECE cell differentiation is maintained in culture. In addition, the cells possess a high affinity, limited capacity binding site for estradiol that has a Kd of 1.2 +/- 0.1 nM. This system is likely to provide a useful model for the study of sex steroid regulation of normal ectocervical epithelial cell function.

Cells, Cultured↗
PubMed1990

Myometrial oxytocin receptors levels in the pregnant rat are higher in distal than in proximal portions of the horn and correlate with disparate oxytocin responsive myometrial contractility in these segments.

Distal (D) segments of the pregnant rat uterine horn express myometrial oxytocin receptors (MORs) earlier than proximal (P) segments (day 18 vs. 20, respectively); the levels in D segments remain higher than in P segments throughout days 21-22 and correlate with the segment-specific myometrial sensitivity to oxytocin. While progesterone (P4) had no effect on MOR levels, RU486 increased (t1/2 6-12 h) MOR levels both in D and P segments, particularly in days 12-17, and the levels in the P segment equaled those in the D segment. Estradiol had no effect on MOR levels in days 20-22; in days 16-19 estradiol increased MOR levels particularly in the P segment, and the levels in the latter were higher than in the D segment. Capillary plasma P4 levels were higher in P vs. in D myometrial segments. These results indicate, in the pregnant rat, a local uterine control of D greater than P MOR expression by P4 withdrawal beginning in day 18. We hypothesize that the D greater than P MOR expression determines a role for oxytocin in initiating myometrial contractions in the D segment, while in active labor another class of agent(s) assume that function in more proximal segments.

Animals↗
PubMed1990

Cultured human ectocervical epithelial cell differentiation is regulated by the combined direct actions of sex steroids, glucocorticoids, and retinoids.

During the menstrual cycle, the ectocervical epithelium undergoes a cyclic change in differentiation that is correlated with changes in the circulating levels of estrogens and progestins. To better understand the mechanisms underlying this regulation, we have developed an ectocervical epithelial cell (ECE cell) culture system that responds in a physiological manner to stimulation by estrogens and progestins. We have recently proposed that four classes of hormones (retinoids, estrogens, progestins, and glucocorticoids) may play an important role in regulating differentiation. In the present paper we test this hypothesis directly by making detailed dose-response curves. Our results demonstrate that estrogen increases ECE cell differentiation, as measured by release of cornified envelopes (superficial cells), while progesterone decreases envelope production. The effects are dose dependent and within the expected physiological range (0.01-10 nM estrogen; 0.1-100 nM progesterone). Very low concentrations of Ro 13-6298 (0.01-10 nM), a synthetic retinoid, decreased envelope production, while hydrocortisone (0.1-50 nM) increased envelope production and cell growth. Importantly, agents that enhance envelope production are neutralized by agents that reduce envelope formation and vice versa. Based on these findings we conclude 1) that the differentiation-enhancing actions of glucocorticoids and estrogens can be antagonized by either progestins or retinoids, and 2) that glucocorticoids and retinoids are likely to determine the ECE cell differentiation set-point in vivo, with the sex steroids directly modulating the phenotype of the ECE cells around this set-point during the menstrual cycle. Moreover, these results appear to explain some of the clinical descriptions of changes in ectocervical cell morphology resulting from hyper- and hypoestrogenic stimulation.

Benzoates↗
PubMed1989

In vitro fertilization (IVF)-surrogacy: application of IVF to women without functional uteri.

Women with absent or dysfunctional uteri consented to controlled ovarian stimulation, ovum aspiration, in vitro fertilization, and embryo culture. Cleaving preembryos were transferred to recipient (surrogate) women whose menstrual cycles were in approximate synchrony with the ovum donor. None of the embryo recipients received medication. Six cases are described, resulting in one spontaneous loss at 6 weeks, four full-term deliveries, and one ongoing pregnancy. HLA typing demonstrated all babies to be genotypic offspring of the gamete donors.

Female↗
PubMed1989

Biosynthesis and physiologic effects of estrogen and pathophysiologic effects of estrogen deficiency: a review.

Women are increasingly spending more years of their lives beyond the menopause, which places them at risk for various health problems due to estrogen deficiency. Tissues and organs with estrogen receptors such as the ovaries, endometrium, vaginal epithelium, hypothalamus, urinary tract, and skin are directly affected by a lack of estrogen production. Other tissues in which estrogen receptors have not been consistently identified, such as bone, are also affected by waning levels of estrogen. The postmenopausal woman frequently experiences neuroendocrine changes (hot flashes) that often dissipate over time and a steady rise in her risk of cardiovascular disease, which approaches that in men of comparable age.

Estrogens↗
PubMed1989

Preliminary experience with in vitro fertilization-surrogate gestational pregnancy.

This report documents the medical details and 3-year follow-up evaluation of the infertile and surrogate couples involved in the first successful in vitro fertilization gestational surrogate pregnancy and summarizes clinical experience and outcome of all patients treated to date. Results of the first 28 couples treated are presented. The pregnancy rate for 39 cycles reaching attempts at oocyte retrieval is 18%. The procedural aspects, ethical issues, legal issues, and subsequent program development are summarized. Recommendations are of a similar program. There are numerous potential pitfalls and traps for the unwary, but our experience has thus far been gratifyingly positive, and we endorse the further provision, observation, and documentation of this controversial approach to the care of the infertile couple.

Demography↗
PubMed1989

Retinoids, sex steroids and glucocorticoids regulate ectocervical cell envelope formation but not the level of the envelope precursor, involucrin.

In spite of extensive study of the reproductive tract, little knowledge is available regarding the function of ectocervical epithelial (ECE) cells. In the present study we utilized a feeder layer of 3T3 cells to grow homogeneous cultures of human ectocervical epithelial cells and demonstrated the presence of the cornified envelope precursor, involucrin. Treatment of these cultures with 1 nM Ro 13-6298, a synthetic analogue of trans-retinoic acid, suppresses envelope formation 6-fold with half-maximal suppression at 0.005-0.01 nM. Treatment with 1 microM hydrocortisone elevates envelope production 2.5-fold. Sex steroids also regulate desquamation: 10 nM diethylstilbestrol, a synthetic estrogen, increases envelope levels 2- to 3-fold, while 300 nM progesterone reduces envelope production 2- to 3-fold. In spite of the retinoid-, glucocorticoid- and sex-steroid-stimulated changes in envelope production, the level of the envelope precursor, involucrin, remains constant. Our results suggest: (1) that, in vivo, ectocervical cell squame formation is regulated by the combined direct action of estrogens, progestins, glucocorticoids and retinoids; and (2) that envelope formation is not regulated by changes in the cellular content of the envelope precursor, involucrin. We present a model summarizing the estrogen, progestin, glucocorticoid and retinoid effects on ectocervical epithelial cell function.

Benzoates↗
PubMed1987

Transdermal estradiol overall safety profile.

The results of both single- and multicenter clinical studies have revealed that the transdermal therapeutic system of estrogen administration (Estraderm, CIBA Pharmaceutical Co., Summit, New Jersey) is both effective and well tolerated. In contrast to oral conjugated estrogens, the patch has no effect on certain liver proteins. Safety variables measured during one study showed no biochemical changes. Moderate bleeding has occurred in some patients with an intact uterus but can be controlled by the addition of a progestogen. The incidence of endometrial hyperplasia and breast tenderness has been relatively low, and minor side effects (such as fluid retention) have been limited. Several investigators have evaluated skin irritation resulting from the systems. Some erythema has been reported, but serious ulcerations or sloughing did not occur. A survey of patient attitudes comparing oral administration and transdermal systems indicated a preference for the transdermal method.

Administration, Cutaneous↗