Ruth T. Savoy-Moore

The effects of long-term androgen treatment on the ovary

Ten patients with female gender dysphoria were treated with exogenous androgen (testosterone [T] enanthate USP) and underwent sex reassignment surgery. Histologic changes of the ovaries of this treated group were studied and compared with those of patients with polycystic ovarian syndrome (PCO) and a normal control group. Significant differences among groups were observed for thickness of the tunica albuginea (639.8 +/- 56.5 micron, 529.2 +/- 59.3 micron, and 170.1 +/- 29.8 micron in the exogenous androgens, PCO, and normal groups, respectively), basal membrane thickness (72.8 +/- 2.8 micron, 46.2 +/- 4.2 micron, and 25.2 micron), number of cystic follicles (2.0 +/- 0.4, 5.8 +/- 0.7, and 1.8 +/- 0.8), and T and luteinizing hormone concentrations. Theca cell hyperplasia was present only in the PCO group. It is concluded that exogenous androgen can thicken the tunica albuginea and basal membrane and that these histologic changes are similar to those seen in PCO ovaries under excess endogenous androgen production.

Effects of oocyte exposure to local anesthetics on in vitro fertilization and embryo development in the mouse

The effect on fertilization and development of local anesthetics routinely used during ultrasound-guided oocyte retrieval in women undergoing in vitro fertilization was examined in a mouse in vitro fertilization system. Mouse oocytes were exposed in vitro to lidocaine, chloroprocaine, and bupivacaine at concentrations of 0 (control), 0.01, 0.1, 1.0, 10.0, 100.0 micrograms/mL for 30 min, washed, and then inseminated. In vitro oocyte fertilization at 24 and 48 h and embryo development at 72 h were determined. Bupivacaine adversely affected mouse in vitro fertilization and embryo development only at the highest exposure concentration, 100 micrograms/mL, while lidocaine and chloroprocaine produced adverse effects at concentrations as low as 1.0 and 0.1 microgram/mL, respectively. Furthermore, an adverse dose-related effect on fertilization and embryo development was shown for lidocaine and chloroprocaine, but not for bupivacaine. These data demonstrate that the local anesthetics, lidocaine (L), chloroprocaine (C), and bupivacaine (B), adversely affect mouse in vitro fertilization and embryo development in the order of C greater than L greater than B.

Alcohol inhibition of suckling-induced prolactin release in lactating rats: threshold evaluation.

Prolactin release in response to suckling was examined in primiparous lactating rats two hours after alcohol administration. Litters were adjusted to eight pups on lactation day 2 and dams were implanted with an atrial catheter on day 6. On day 10, pups were separated from the mother at 0800 h. An extension was attached to the catheter at 1100 h. Following removal of a baseline blood sample an hour later, rats were infused with alcohol doses of 0, 0.5, 1.0, 2.0 or 2.5 g/kg body weight. Two hours later, pups were returned to dams. Subsequent blood samples were obtained 10, 30, 60, 120 and 180 min after the onset of suckling. Following 10 min of suckling, plasma prolactin for groups of rats infused with alcohol at 2.0 and 2.5 g/kg body weight were lower than control, 0.5 and 1.0 g/kg groups. The blood alcohol level (BAL) for the 2.0 g/kg group was 94 +/- 8 mg% and for the 2.5 g/kg group was 162 +/- 4 mg%. After 30 min, the BAL for the 2.5 g/kg group was 134 +/- 5 mg% and plasma prolactin was suppressed in this group compared to control, 0.5 and 1.0 g/kg groups. The BAL for the 2.0 g/kg group after 30 min of suckling was 74 +/- 9 mg% but prolactin was not significantly lower than controls. We conclude that in rats, alcohol inhibition of suckling-induced prolactin release is directly correlated to the BAL. The threshold BAL which effectively inhibits this prolactin release is lower than the human legal intoxication level.

Attenuation of the magnitude of suckling-induced prolactin release with advancing lactation: mechanisms.

To study why suckling-induced plasma prolactin levels decline in magnitude with advancing lactation, we examined prolactin release in lactating rats following suckling and pharmacologic manipulations during early, mid- and late lactation. On day 2 of lactation, litters were adjusted to 8 pups. On day 3, dams were implanted with an atrial catheter and experiments were conducted on lactation days 5, 11 and 17. To examine suckling-induced prolactin release, pups were removed at 0800 h, an extension was attached to the catheter at 1100 h, and pups returned to dams at 1200 h. Blood samples were obtained before, and at 10, 30, 60, 90 and 120 min after suckling started. Prolactin responses to sulpiride and thyrotropin releasing hormone (TRH) administration were studied in lactating rats separated from their litters for 4 hours. Blood samples were obtained before, and at 10, 30, 60 and 90 min after sulpiride (10 or 40 micrograms/kg BW) and 5, 10, 20 and 30 min after TRH (1 or 4 micrograms/kg BW) in rats pretreated with sulpiride. Prolactin release in response to suckling, administration of sulpiride or sulpiride and TRH diminished as lactation advanced. From these results, we conclude that refractoriness in anterior pituitary lactrotropes to prolactin-releasing stimuli is at least partially responsible for the decline in suckling-induced prolactin release with advancing lactation.

Alcohol Effects on TRH-Induced Prolactin Response in Lactating Rats: In Vivo and In Vitro Studies

The site of action of alcohol in inhibiting suckling-induced prolactin release in lactating rats was examined by in vivo and in vitro studies. In vivo, sulpiride- and thyrotropin-releasing hormone (TRH)-induced prolactin release was studied in lactating rats separated from their litter. On day 7, dams were implanted with an atrial catheter. On day 10, pups were removed from dams at 0800 h and, after 5 h, an extension was attached to the catheter. An hour later, a baseline blood sample was removed and was followed by sulpiride (40 micrograms/kg) administration. Additional blood samples were withdrawn over 1 h. After the 60-min sample, sulpiride-administered rats were infused with 0.0, 1.0, or 2.0 g/kg b.wt. alcohol. Following alcohol, a postinfusion blood sample was removed, TRH (4.0 micrograms/kg) was administered, and subsequent blood samples were obtained 5, 10, 20, and 30 min after TRH. For in vitro studies, cells from lactating rats in midlactation were enzymatically dissociated, plated, and on culture day 5 were exposed to 0 or 10 nM TRH. Each set of cells were additionally exposed to 0, 100, or 300 mg% alcohol and media harvested after 4 h. In a subsequent study, plated cells were exposed to increasing doses of TRH in the presence of 0, 100, or 300 mg% alcohol and media harvested as above. Prolactin in plasma (in vivo studies) and medium (in vitro studies) was measured by RIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Human granulosa-luteal cell response to vinblastine exposure in vitro

We examined the response of isolated human granulosa-luteal cells (HGLCs) to a cancer chemotherapeutic agent, vinblastine (VLB), that has been implicated in ovarian failure during treatment for Hodgkins disease. VLB doses of 1.0 micrograms/mL for 4 h or 0.1 micrograms/mL for 24 h reduced HGLC progesterone production during exposure. The effect of high doses (10.0 and 100.0 micrograms/mL) persisted for at least 1 day after exposure. Previous 24 h, but not 4 h, high-dose VLB exposure reduced subsequent progesterone release in response to 10 IU of human chorionic gonadotropin (hCG). Without hCG stimulation, only cells previously exposed to 100.0 micrograms/mL had persistently reduced progesterone release. We conclude that HGLCs can completely recover from a short exposure to VLB, but longer exposures to 10.0 and 100.0 micrograms/mL are detrimental to their hormone secreting capacity.

The effect of cocaine on oocyte development and the follicular microenvironment in the rabbit**Presented in part at the 36th Annual Meeting of the Society for Gynecological Investigation, San Diego, California, March 15 to 18, 1989; and at the 45th Annual Meeting of The American Fertility Society, San Francisco, California, November 11 to 16, 1989.

We examined the effects of cocaine exposure in the rabbit on in vitro oocyte development and on steroidal content of follicular fluid (FF) and serum progesterone (P). Cocaine hydrochloride (0, 10, 20, 40, or 80 mg/kg) was administered daily subcutaneously for 5 days to New Zealand White female rabbits before superovulation. On the last day of cocaine administration, animals were given human chorionic gonadotropin intravenously, and laparotomy was performed 6 to 8 hours later. During laparotomy, ovaries were removed, the number of follicles recorded, oocytes retrieved, and FF was obtained. In vitro fertilization (IVF) was then performed on the oocytes and the rate of cleavage observed. For all cocaine dosage groups, no differences were observed in the number of follicles present, number of oocytes retrieved, or IVF and cleavage rates. Cocaine did, however, decrease periovulatory serum P, and FF P, whereas FF estradiol concentrations increased. This suggests that short-term cocaine exposure affects the follicular steroid milieu, possibly by delaying granulosa cell luteinization.