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Web Topic 6.4: Organizational and Activational Effects of Hormones on the Brain

[Referenced on textbook p. 174]

In the years since the pioneering studies on the organizational and activational effects of gonadal hormones on the brain (as described in the textbook), we have gained some insight into how these effects occur. With regard to organizational effects, it is striking that the sensitive periods for the organization of sexual behaviors tend to coincide with the sensitive periods for the development of sexually dimorphic structures such as SDN-POA. Thus, at least in part, early hormone exposure probably organizes later behaviors by helping set up the brain systems that mediate these behaviors. At the most obvious level, these organizational effects would include the formation of nuclei such as SDN-POA, but they probably also include more subtle effects—on a neuron’s synaptic connections and neurotransmitter synthesis, for example.

How do hormones activate sex-specific behaviors in adulthood? The best-studied animal model is the lordosis reflex, which has been the focus of a research group at Rockefeller University led by Donald Pfaff (Weil et al., 2010). Female rats exhibit lordosis during only one night of their 4- or 5-day ovarian cycle. The capacity to show the reflex is turned on by two hormones acting in combination: rising estrogen levels during the early part of the cycle, followed by a surge of progesterone near the time of ovulation. These hormones act on the ventromedial nucleus of the hypothalamus (VMN) to facilitate the reflex.

The effect of these hormones on the VMN involves two types of actions. In the first type, the hormones bind to the “classic” steroid receptors and thus regulate gene activity. For example, the binding of estrogen to its receptor causes an increase in the activity of the gene for the progestin receptor, so the neurons of the VMN become more sensitive to progesterone. Other genes turned on by estrogen probably include genes concerned with cell growth, because the dendrites of the VMN neurons (the cytoplasmic extensions that receive synaptic inputs; see Chapter 4) lengthen significantly during the 2 days of the cycle when the cells are exposed to estrogens.

In the second type of action, the hormones bind to “non-classic” steroid receptors in the plasma membranes of the VMN neurons. Some of these receptors are closely associated with synapses and may directly modulate the responsiveness of the VMN neurons to incoming signals, such as the sensory signals generated when the female rat is mounted by a male. Other membrane receptors activate an internal cascade of second messengers, which in turn affect the cells’ responsiveness by a variety of means (Kow & Pfaff, 1998). The net effect of all these processes is to ensure that the female rat will respond to mounting by showing lordosis behavior, but only during the narrow window in her estrous cycle when insemination by a male can lead to fertilization.


Kow, L. M. & Pfaff, D. W. (1998). Mapping of neural and signal transduction pathways for lordosis in the search for estrogen actions on the central nervous system. Behavioural Brain Research 92: 169–180.

Weil, Z. M., Murakami, G. & Pfaff, D. W. (2010). Reproductive behaviors: new developments in concepts and in molecular mechanisms progress in brain research, Luciano Martini, editor, January 19, 2010. Prog Brain Res 181: 35–41.