Androgen support of lacrimal gland function.

The effects of dihydrotestosterone (DHT) (1 mg/kg) on biochemical parameters related to lacrimal secretion, basal tear flow rate, and pilocarpine-stimulated lacrimal gland fluid secretion, in mature ovariectomized rabbits were studied. The effects of the synthetic estrogen diethylstilbestrol (DES) (100 micrograms/kg), on lacrimal gland biochemical parameters in normal mature female rabbits was also studied. Ovariectomy decreased the total serum levels of testosterone (T) by 88.5% and androstenedione by 35.9%, without changing the levels of dehydroepiandrosterone (DHEA) of its sulfate. Ovariectomy caused a significant regression of the lacrimal glands, decreasing total DNA by 35%, and total protein by 22%. DHT treatment of ovariectomized animals prevented lacrimal gland regression, increasing total gland DNA (31%) and total protein (18%). DHT treatment also increases Na+, K(+)-ATPase activity (29%) and beta-adrenergic receptor binding sites (23%) compared to the ovariectomized group. DHT increased pilocarpine stimulated lacrimal gland fluid secretion (13.26 +/- 1.47 microL/min) compared to the ovariectomized group (7.72 +/- 0.41 microL/min), but DHT treatment paradoxically decreased basal tear flow rate (1.02 +/- 0.04 microL/min) as compared to the ovariectomized rabbits (1.96 +/- 0.12 microL/min). DES decreased the total serum T from 59.33 +/- 10.54 pg/mL to 21.5 +/- 6.06 pg/mL. DES decreased total Na+,K(+)-ATPase by 12% and increased beta-adrenergic receptor binding sites by 83.3%. These results suggest that androgens play a major role in supporting lacrimal gland secretory function. Additionally, they suggest that estrogens may influence certain aspects of lacrimal functions, although it is not clear to what extent those actions are elicited directly or indirectly.

Prorenin is elevated in polycystic ovary syndrome and may reflect hyperandrogenism.

OBJECTIVE: To examine the null hypothesis that women with polycystic ovary syndrome (PCOS) produce similar levels of prorenin and other components of the ovarian-derived prorenin to angiotensin cascade (ODPAC) at baseline and after stimulation with clomiphene citrate (CC) or hMG when compared with normal age- and weight-matched ovulatory controls. DESIGN: Prospective controlled clinical trial. SETTING: Infertility clinic in a university-based county hospital and a hospital-based private infertility practice. PATIENTS: Twenty-eight infertile women aged 18 to 35 years. Thirteen patients were diagnosed with PCOS. Fifteen normal ovulatory patients who were matched for age and weight served as controls. INTERVENTIONS: Twenty patients were stimulated with CC and eight were stimulated with hMG. MAIN OUTCOME MEASURES: Serum E2, P, T, androstenedione (A), DHEAS, LH, FSH, and plasma prorenin, active renin, and angiotensin II (Ang II) were measured at baseline and during the preovulatory and midluteal phases of the stimulation cycles. RESULTS: Baseline plasma prorenin in PCOS was higher than that of follicular phase controls. Plasma prorenin correlated significantly with peripheral androgen levels. Prorenin, active renin, and Ang II increased in response to gonadotropins with the largest increases occurring in control patients receiving CC. An association was seen between ovulation with CC and lower baseline levels of active renin. CONCLUSIONS: The null hypothesis was rejected. Infertile women with PCOS have higher baseline prorenin levels when compared with age- and weight-matched ovulatory controls. There is a significant correlation between prorenin and the peripheral levels of androgens produced during ovarian stimulation. Baseline active renin levels may be predictive of ovulation with CC.

Inhibition of ovarian-derived prorenin to angiotensin cascade in the treatment of ovarian hyperstimulation syndrome.

The purpose of this experiment was to determine whether use of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, would prevent the occurrence of ovarian hyperstimulation syndrome (OHSS) in the rabbit model. A total of 20 adult female New Zealand white rabbits were studied. All rabbits received 75 IU of human menopausal gonadotrophin s.c. each day for 7 days. On day 8, all rabbits received 2500 IU of human chorionic gonadotrophin (HCG). Ten rabbits were randomly chosen to receive enalapril orally. Five received 1 mg/kg of enalapril and five received 2 mg/kg of enalapril twice daily. The remainder received placebo orally twice daily. On day 10, all rabbits underwent surgical exploration. Total body weight was found to increase significantly in the placebo group (by 293 g, P < 0.001) but not in either group receiving enalapril. Haematocrit also increased significantly in the placebo group (by 3%, P < 0.013) but not in the enalapril groups. Ovarian weights were highest for the 2 mg/kg enalapril group (5.80 +/- 0.52 g), followed by the 1 mg/kg enalapril group (3.64 +/- 0.45), and least for the placebo group (2.69 +/- 0.17). All 10 placebo rabbits met criteria for severe OHSS whereas only six in the enalapril groups did. We concluded that angiotensin II may play a significant role in the development of weight gain, third space fluid accumulation and intravascular fluid depletion in OHSS. ACE inhibition resulted in a 40% decrease in the incidence of OHSS in the rabbit model.