Epitestosterone: A Potential New Antiandrogen

Epitestosterone (EpiT) is the 17α-hydroxy epimer of testosterone (T) and a natural steroid metabolite. It has previously been shown to be a 5α-reductase inhibitor. We have studied EpiT as an antiandrogen using the hamster flank organ model. One-centimeter silastic capsules of crystalline T or dihydrotestosterone (DHT) were implanted subcutaneously in female Golden Syrian hamsters to provide continuous androgenic stimulation. After 3 weeks, the pigmented spot was measured and the flank organs were fixed for histologic sectioning. The maximum surface area (SA) from a central section of the sebaceous gland and the diameter of hair follicles were measured using a computerized digitizing tablet. Following T and DHT, respectively, there was a significant increase in pigmented spot size (656/382%), sebaceous gland SA (210/315%), and mean hair follicle diameter (80/56%). A 1-cm capsule of EpiT alone had no androgenic effect. Five- and ten-fold doses of EpiT were implanted with T or DHT. Epitestosterone significantly inhibited tile T-dependent stimulation of pigment, sebaceous gland, and hair follicle at either 5- and/or 10-fold excess doses. Additionally, a 10-fold dose of EpiT also inhibited DHT-dependent stimulation of all 3 cutaneous structures. We conclude that EpiT was effective as an antiandrogen and had no intrinsic androgenic activity in the hamster flank organ. It probably functions both as a competitive inhibitor of the androgen receptor and as a 5α- reductase inhibitor. Pigment and sebaceous gland growth were more sensitive than the hair follicle to androgen inhibition by EpiT at the time and doses tested

Hair Follicle Response of the Golden Syrian Hamster Flank Organ to Continuous Testosterone Stimulation Using Silastic Capsules

The hamster flank organ has served as a model to study androgen-dependent responses of the skin, but the quantitative response of hair follicles to androgenic stimulation has been neglected. We assayed the hair follicle response to testosterone (T) and compared it to the response of the sebaceous glands and of the dermal pigment in the Golden Syrian hamster flank organ. Because of biologic variation in male animals and uneven absorption of hormone from parenteral injections, we implanted silastic capsules 0.25, 0.5, 1, and 2 cm in length filled with crystalline T sub-cutaneously into female hamsters for 6 weeks. Hair follicle response to T was more sensitive than sebaceous gland or pigment. Diameters of hairs under the sebaceous gland increased significantly from control values of 27.7 ± 1.0 p.m to 38.0 ± 1.6 μm at the lowest dose of T tested, the 0.25-cm capsule (p < 0.001). There was an increase in the absolute number of hairs under the sebaceous gland as the flank organ enlarged, from 27.9 ± 9.9 control to 55.3 ± 5.8 with the 2-cm T capsule. There was no concomitant increase in hair density, 14.4 ± 3.5 hairs/mm control vs 12.5 ± 1.1 hairs/mm with the 2-cm capsule. Hair follicles lateral to the sebaceous gland did not show the same response to androgen stimulation. Sebaceous gland and pigmentation responded in a dose-dependent fashion, the maximum effect being achieved with a 1-cm T capsule.We conclude that T affects hair by specifically stimulating growth of individual hairs physically under the sebaceous gland. As the whole flank organ enlarges more hairs are recruited to become larger but 110 new follicles appear. These studies also confirm that there are different sensitivities to androgen within the various androgen-dependent components of the hamster flank organ, with increase in hair diameter being highly sensitive. This model should be useful for the specific and quantitative assessment of androgenic and antiandrogenic substances on hair growth and ultimately be useful for therapy of hirsutism

Low-Loss Vertical MMI Coupler for 3D Photonic Integration

A polymer vertical multi-mode interference coupler with device losses below 1.2 dB for a vertical centre-to-centre waveguide distance of 7.2 μm is presented

High Isolation Optical Isolator: A new Building Block for PolyBoard Photonic Integrated Circuits

We experimentally demonstrate a polymer-based optical isolator, hybridly integrating two GRIN lenses and a Faraday Rotator. An isolation of 20 dB over a bandwidth of 80 nm was achieved, with a peak isolation of 33 dB