A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome.

• Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a "hyperplastic" theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Adipocytes

metabolism

pathology

Androgens

pharmacology

Animals

Aromatase Inhibitors

pharmacology

Body Composition

drug effects

physiology

Body Weight

drug effects

physiology

Dihydrotestosterone

pharmacology

Disease Models

Animal

Estrous Cycle

metabolism

Female

Magnetic Resonance Imaging

Mesentery

metabolism

pathology

Muscle

Skeletal

pathology

Nitriles

pharmacology

Organ Size

Ovary

metabolism

pathology

Polycystic Ovary Syndrome

drug therapy

metabolism

pathology

Rats

Rats

Wistar

Testosterone

blood

Triazoles

pharmacology

MEDICINE

Publikations- och innehållstyp

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