Endocrine organization of sex differences in psychology and behavior: Evidence from isolated GnRH deficiency
Restricted (Penn State Only)
- Author:
- Shirazi, Talia
- Graduate Program:
- Anthropology (PHD)
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 26, 2021
- Committee Members:
- Asher Rosinger, Major Field Member
Sonia Cavigelli, Outside Field Member
Mark Shriver, Major Field Member
Suzy Scherf, Outside Unit & Field Member
David Puts, Chair & Dissertation Advisor
Mary Katherine Shenk, Program Head/Chair - Keywords:
- hormones
organizational effects
behavioral endocrinology
isolated GnRH deficiency
androgens
estrogens
puberty - Abstract:
- Prenatal and perinatal gonadal hormones are instrumental in the sexual differentiation of reproductive physiology, psychology, and behavior. As evidenced by research using experimental animal models and human disease models wherein hormone action is naturally and congenitally altered, perturbations in hormone action during the perinatal period exert permanent, or organizational, effects on behavior across the lifespan. It has recently been suggested that puberty represents a second period wherein hormone action organizes behavior, and moreover, that the ability of hormones to exert these effects decreases across the pubertal window. This dissertation considers the human disease model isolated gonadotropin releasing hormone (GnRH) deficiency (IGD) to answer two broad questions in behavioral neuroendocrinology: 1) What is the enduring effect of chronically low steroid hormone exposure from mid-gestation to adolescence on psychological phenotypes in adulthood? and 2) Does the ability of hormones to organize psychology and behavior differ across pubertal development? IGD is characterized by nonfunctional or absent GnRH neurons, rendering people with the condition unable to produce gonadotropins and gonadal hormones. Hormone action during the first trimester of gestation, however, is largely sex-typical, as placental human chorionic gonadotropin (hCG) stimulates the production of androgens and estrogens. The drop in hCG around the beginning of the second trimester of gestation marks the beginning of chronically low gonadal hormone action, which persists until a hormone replacement therapy regimen is started in adolescence or adulthood. IGD thus serves as a unique human model to investigate the consequences of low-to-absent perinatal hormone action, as well as the influence of the timing of sex steroid exposure around puberty. The first set of studies in this dissertation examines the effect of chronically low hormone action from the second trimester of gestation until puberty, by comparing people with and without IGD on two of the most sexually dimorphic phenotypes in humans: childhood gender role behaviors and sexual orientation. We find compelling evidence that low androgens are associated with higher childhood gender nonconformity in men (Chapter 2), and that low estrogens are associated with lower levels of androphilia in women (Chapter 3). These data add to our understanding of the timing of the prenatal window in which hormone action organizes the neural substrates of sexually dimorphic psychology and behavior, and of the important and unique roles of androgen and estrogen action. The second set of studies examines associations between pubertal timing and adult phenotypes that exhibit sex differences that either emerge or expand around puberty. Whereas null associations between pubertal timing and adult phenotypes would suggest a constant sensitivity to hormone-driven organization across this critical period, associations between these two variables would suggest differential sensitivity. We find that earlier pubertal timing is associated with higher male-typicality in male-typed tests of spatial cognition in men (Chapter 4), and with higher levels of psychosexuality in both men and women (Chapter 5). Taken together, the studies presented in this dissertation shed light on the importance of hormone action during critical developmental windows in permanently modulating sexually differentiated psychology and behavior. We find that hormone action after the first trimester of gestation exerts significant organizational effects, though different hormones may drive the development of different phenotypes. We also find evidence to suggest that the ability of hormones to exert organizational effects differs across pubertal development. All studies highlight the utility of IGD as a human disease model to clarify effects of chronically low hormone action and pubertal timing ultimately to better understand human psychobehavioral variation.