Estrenes for inducing hypothalamic effects

A = 1, 3, 5(10),16-Estratetraen-3-yl acetate
B = Androsta-4,16-dien-3-one (i.e. A1)
C = 1,3,5(10),16-Estratetraen-3-ol (i.e. EST)
D = 3-Methoxy-Estra-1,3,5(10),16-tetraene
E = Androsta-4,16-dien-3.alpha.-ol
F = Androsta-4,16-dien-3.beta.-ol
G = Androst-4-en-3-one
H = Androsta-4,16-diene-3,6-dione
J = 10,17-Dimethylgona-4,13(17)-dien-3-one
K = 1,3,5(10),16-Estratetraen-3-ol-methyl ether [E0723-080 Steraloids]
L = 1,3,5(10),16-Estratetraen-3-yl-propionate
M = 1,3,5(10)-Estratrien-3-ol [R187798 (Aldrich)]

E12/N1 = Estra-1,3,5(10),16-tetraen-3,6.beta.-diol
E8/N1 = 3-MethoxyEstra-2,5(10),16-triene
E7/N1 = 10-HydroxyEstra-4,16-dien-3-one

OE = olfactory epithelium
CNS = central nervous system
EVG = Electro-vomeronasogram
EOG = Electro-olfactgram

EFFECTS ON THE EVG

  • A, C and D produced significant effects, that were consistent in all individual cases (males).

  • Vomeropherins active in male subjects produced larger responses than the diluent. B, F and similar concentrations of olfactants induced significantly reduced responses in the male VNO.

  • Among the vomeropherins, F produced the most significant differences within the group (females). Here, A induced a small effect that was significantly different from F.

  • In both populations of subjects, active vomeropherins induced receptor responses having large standard deviations. When the frequency distribution of the effects of A and F was studied in males and females respectively, we found a bimodal distribution. The significance of this observation is being studied at this point.

E, a stereoisomer of F, does not stimulate the VNO in female subjects while F does. This is a demonstration of the specificity of VNO recognition of vomeropherins. In this regard it is interesting to note that while F is a superior vomeropherin, E generates a stronger olfactory effect than does F.

EFFECTS ON THE EOG

  • In contrast to the sensitivity of the VNO to vomeropherins, the OE is less sensitive to these substances. This is true for both males and females.

  • In this study, B was the only vomeropherin having significant effect in the OE.

  • This finding reveals that at the concentrations used in our study, most vomeropherins are not effective stimulants of the olfactory receptors, but do have a clear effect on vomeronasal receptors.

REFLEX EFFECTS

  • A and C induced a significant increase in skin temperature in 30 male subjects; however D induced significant temperature decrease.

  • In 30 female subjects, B and F evoked a significant increase in skin temperature compared to A and C.

  • In males, A, C and D significantly increased alpha cortical activity (D and A evoked the strongest effect).

  • In females, B or F applied to the VNO increased alpha cortical independent of the response of olfactory receptors.

  • The steroid E12/N1 exhibited the best EEG-alpha activity in men. The steroid E8/N1 exhibited the best EEG-beta activity in men.

  • The steroid E7/N1 exhibited the best EEG-alpha activity in women. Additionally, it is noted that E7/N1 exhibited excellent organ response, as shown by the EVG data, in both men and women, but there were gender differences in the CNS (high EEG-alpha in women, high EEG-beta in men).

Sexual differences were noted in the specificities and effects of two groups of vomeropherins, A, C and D; and B and F.